rs14920

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001082486.2(ACD):c.1371G>T(p.Pro457=) 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 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 criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.72

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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]. Clinvar id 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/exons	MANE	Protein	UniProt
ACD	NM_001082486.2 linkuse as main transcript	c.1371G>T	p.Pro457=	synonymous_variant	12/12	ENST00000620761.6	NP_001075955.2
CARMIL2	NM_001013838.3 linkuse as main transcript			downstream_gene_variant		ENST00000334583.11	NP_001013860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACD	ENST00000620761.6 linkuse as main transcript	c.1371G>T	p.Pro457=	synonymous_variant	12/12	1	NM_001082486.2	ENSP00000478084	P1	Q96AP0-3
CARMIL2	ENST00000334583.11 linkuse as main transcript			downstream_gene_variant		1	NM_001013838.3	ENSP00000334958	A2	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

GnomAD3 exomes

AF:

0.0345

AC:

8661

AN:

251346

Hom.:

217

AF XY:

0.0349

AC XY:

4740

AN XY:

135858

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 SAS exome

AF:

0.0108

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

Gnomad4 AFR exome

AF:

0.00741

Gnomad4 AMR exome

AF:

0.0231

Gnomad4 ASJ exome

AF:

0.0259

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0109

Gnomad4 FIN exome

AF:

0.0524

Gnomad4 NFE exome

AF:

0.0517

Gnomad4 OTH exome

AF:

0.0426

GnomAD4 genome

AF:

0.0339

AC:

5164

AN:

152328

Hom.:

129

Cov.:

AF XY:

0.0332

AC XY:

2470

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00943

Gnomad4 AMR

AF:

0.0299

Gnomad4 ASJ

AF:

0.0308

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.00870

Gnomad4 FIN

AF:

0.0532

Gnomad4 NFE

AF:

0.0514

Gnomad4 OTH

AF:

0.0393

Alfa

AF:

0.0449

Hom.:

236

Bravo

AF:

0.0317

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.0504

EpiControl

AF:

0.0500

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Dyskeratosis congenita, autosomal dominant 6

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Aug 15, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

1.7

DANN

Benign

0.70

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over