16-67657612-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001082486.2(ACD):c.1371G>T(p.Pro457Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.044 in 1,614,150 control chromosomes in the GnomAD database, including 1,817 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. P457P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.034 ( 129 hom., cov: 33)

Exomes 𝑓: 0.045 ( 1688 hom. )

Consequence

ACD
NM_001082486.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.72

Publications

10 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 links:

CARMIL2 (HGNC:27089): (capping protein regulator and myosin 1 linker 2) This gene encodes a member of the CARMIL (capping protein, Arp2/3, myosin-I linker) family of proteins. The encoded protein interacts with and negatively regulates the heterodimeric capping protein and promotes cell migration. Reduced expression of this gene has been observed in human psoriasis patients. Mutations in this gene cause a human immunodeficiency syndrome characterized by smooth muscle tumors and impaired T-cell function. [provided by RefSeq, May 2017]

CARMIL2 Gene-Disease associations (from GenCC):

severe combined immunodeficiency due to CARMIL2 deficiency
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet

CARMIL2 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=-0.52).

BP6

Variant 16-67657612-C-A is Benign according to our data. Variant chr16-67657612-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 475766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.72 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACD	NM_001082486.2 link	c.1371G>T	p.Pro457Pro	synonymous_variant	Exon 12 of 12	ENST00000620761.6	NP_001075955.2	Q96AP0-3
CARMIL2	NM_001013838.3 link	c.*94C>A		downstream_gene_variant		ENST00000334583.11	NP_001013860.1	Q6F5E8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACD	ENST00000620761.6 link	c.1371G>T	p.Pro457Pro	synonymous_variant	Exon 12 of 12	1	NM_001082486.2	ENSP00000478084.1		Q96AP0-3
CARMIL2	ENST00000334583.11 link	c.*94C>A		downstream_gene_variant		1	NM_001013838.3	ENSP00000334958.5		Q6F5E8-1

Frequencies

GnomAD3 genomes

AF:

0.0339

AC:

5166

AN:

152210

Hom.:

129

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00946

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0300

Gnomad ASJ

AF:

0.0308

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00890

Gnomad FIN

AF:

0.0532

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0514

Gnomad OTH

AF:

0.0398

GnomAD2 exomes

AF:

0.0345

AC:

8661

AN:

251346

AF XY:

0.0349

show subpopulations

Gnomad AFR exome

AF:

0.00843

Gnomad AMR exome

AF:

0.0216

Gnomad ASJ exome

AF:

0.0276

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0501

Gnomad NFE exome

AF:

0.0512

Gnomad OTH exome

AF:

0.0424

GnomAD4 exome

AF:

0.0451

AC:

65931

AN:

1461822

Hom.:

1688

Cov.:

AF XY:

0.0442

AC XY:

32120

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.00741

AC:

248

AN:

33480

American (AMR)

AF:

0.0231

AC:

1033

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0259

AC:

678

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.0109

AC:

938

AN:

86256

European-Finnish (FIN)

AF:

0.0524

AC:

2796

AN:

53370

Middle Eastern (MID)

AF:

0.0336

AC:

194

AN:

5768

European-Non Finnish (NFE)

AF:

0.0517

AC:

57466

AN:

1111996

Other (OTH)

AF:

0.0426

AC:

2575

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

3768

7537

11305

15074

18842

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2108

4216

6324

8432

10540

<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:

0.0339

AC:

5164

AN:

152328

Hom.:

129

Cov.:

AF XY:

0.0332

AC XY:

2470

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00943

AC:

392

AN:

41578

American (AMR)

AF:

0.0299

AC:

458

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0308

AC:

107

AN:

3472

East Asian (EAS)

AF:

0.000771

AC:

AN:

5186

South Asian (SAS)

AF:

0.00870

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0532

AC:

564

AN:

10608

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0514

AC:

3494

AN:

68036

Other (OTH)

AF:

0.0393

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

264

528

792

1056

1320

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0445

Hom.:

307

Bravo

AF:

0.0317

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.0504

EpiControl

AF:

0.0500

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 14, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dyskeratosis congenita, autosomal dominant 6

Benign:2

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Hereditary cancer-predisposing syndrome

Benign:1

Sep 09, 2024

Hereditary Cancer Laboratory, Hospital Universitario 12 de Octubre

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PM2+BP4+BP6+BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

1.7

(source)

DANN

Benign

0.70

PhyloP100

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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