rs72549181

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001082486.2(ACD):c.801C>T(p.Ala267Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000911 in 1,572,944 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A267A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0049 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00048 ( 4 hom. )

Consequence

ACD
NM_001082486.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.412

Publications

1 publications found

Variant links:

Genes affected

ACD (HGNC:25070): (ACD shelterin complex subunit and telomerase recruitment factor) This gene encodes a protein that is involved in telomere function. This protein is one of six core proteins in the telosome/shelterin telomeric complex, which functions to maintain telomere length and to protect telomere ends. Through its interaction with other components, this protein plays a key role in the assembly and stabilization of this complex, and it mediates the access of telomerase to the telomere. Multiple transcript variants encoding different isoforms have been found for this gene. This gene, which is also referred to as TPP1, is distinct from the unrelated TPP1 gene on chromosome 11, which encodes tripeptidyl-peptidase I. [provided by RefSeq, Jul 2008]

ACD Gene-Disease associations (from GenCC):

dyskeratosis congenita, autosomal dominant 6
Inheritance: AR, AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P
hereditary isolated aplastic anemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Hoyeraal-Hreidarsson syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 16-67658583-G-A is Benign according to our data. Variant chr16-67658583-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 542420.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.412 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00495 (753/152268) while in subpopulation AFR AF = 0.0173 (718/41542). AF 95% confidence interval is 0.0162. There are 1 homozygotes in GnomAd4. There are 352 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 4 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACD	NM_001082486.2 link	c.801C>T	p.Ala267Ala	synonymous_variant	Exon 9 of 12	ENST00000620761.6	NP_001075955.2	Q96AP0-3
ACD	NM_022914.3 link	c.792C>T	p.Ala264Ala	synonymous_variant	Exon 9 of 12		NP_075065.3	Q96AP0-2
ACD	NM_001410884.1 link	c.742+137C>T		intron_variant	Intron 8 of 10		NP_001397813.1
ACD	XR_429728.4 link	n.798+137C>T		intron_variant	Intron 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACD	ENST00000620761.6 link	c.801C>T	p.Ala267Ala	synonymous_variant	Exon 9 of 12	1	NM_001082486.2	ENSP00000478084.1		Q96AP0-3

Frequencies

GnomAD3 genomes

AF:

0.00495

AC:

753

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0173

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00151

AC:

329

AN:

217814

AF XY:

0.00110

show subpopulations

Gnomad AFR exome

AF:

0.0180

Gnomad AMR exome

AF:

0.00120

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000202

Gnomad OTH exome

AF:

0.000585

GnomAD4 exome

AF:

0.000479

AC:

680

AN:

1420676

Hom.:

Cov.:

AF XY:

0.000393

AC XY:

276

AN XY:

701760

show subpopulations

African (AFR)

AF:

0.0160

AC:

521

AN:

32554

American (AMR)

AF:

0.00135

AC:

AN:

40824

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22922

East Asian (EAS)

AF:

0.00

AC:

AN:

39372

South Asian (SAS)

AF:

0.0000127

AC:

AN:

79024

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51598

Middle Eastern (MID)

AF:

0.000902

AC:

AN:

5544

European-Non Finnish (NFE)

AF:

0.0000174

AC:

AN:

1090302

Other (OTH)

AF:

0.00135

AC:

AN:

58536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

111

148

185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00495

AC:

753

AN:

152268

Hom.:

Cov.:

AF XY:

0.00473

AC XY:

352

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0173

AC:

718

AN:

41542

American (AMR)

AF:

0.00157

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68016

Other (OTH)

AF:

0.00237

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

103

137

171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00285

Hom.:

Bravo

AF:

0.00541

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Feb 12, 2022

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

ACD-related disorder

Benign:1

Jul 31, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dyskeratosis congenita, autosomal dominant 6

Benign:1

Jan 18, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.7

(source)

DANN

Benign

0.63

PhyloP100

-0.41

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over