Variant 1-40059439-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006367.4(CAP1):c.93T>C(p.Tyr31Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00393 in 1,607,522 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0099 ( 18 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 28 hom. )

Consequence

CAP1
NM_006367.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.248

Variant links:

Genes affected

CAP1 (HGNC:20040): (cyclase associated actin cytoskeleton regulatory protein 1) The protein encoded by this gene is related to the S. cerevisiae CAP protein, which is involved in the cyclic AMP pathway. The human protein is able to interact with other molecules of the same protein, as well as with CAP2 and actin. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2016]

CAP1 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=-0.58).

BP6

Variant 1-40059439-T-C is Benign according to our data. Variant chr1-40059439-T-C is described in ClinVar as [Benign]. Clinvar id is 773108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.248 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0099 (1508/152320) while in subpopulation AFR AF= 0.0298 (1238/41562). AF 95% confidence interval is 0.0284. There are 18 homozygotes in gnomad4. There are 745 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1508 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAP1	NM_006367.4 link	c.93T>C	p.Tyr31Tyr	synonymous_variant	2/13	ENST00000372805.8	NP_006358.2	Q01518-1D3DPU2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAP1	ENST00000372805.8 link	c.93T>C	p.Tyr31Tyr	synonymous_variant	2/13	1	NM_006367.4	ENSP00000361891.3		Q01518-1

Frequencies

GnomAD3 genomes

AF:

0.00989

AC:

1505

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0298

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00700

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00185

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00473

AC:

1180

AN:

249288

Hom.:

AF XY:

0.00447

AC XY:

605

AN XY:

135252

show subpopulations

Gnomad AFR exome

AF:

0.0321

Gnomad AMR exome

AF:

0.00406

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00650

Gnomad FIN exome

AF:

0.000510

Gnomad NFE exome

AF:

0.00271

Gnomad OTH exome

AF:

0.00331

GnomAD4 exome

AF:

0.00331

AC:

4817

AN:

1455202

Hom.:

Cov.:

AF XY:

0.00334

AC XY:

2417

AN XY:

724320

show subpopulations

Gnomad4 AFR exome

AF:

0.0312

Gnomad4 AMR exome

AF:

0.00412

Gnomad4 ASJ exome

AF:

0.000613

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00643

Gnomad4 FIN exome

AF:

0.000337

Gnomad4 NFE exome

AF:

0.00241

Gnomad4 OTH exome

AF:

0.00470

GnomAD4 genome

AF:

0.00990

AC:

1508

AN:

152320

Hom.:

Cov.:

AF XY:

0.0100

AC XY:

745

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0298

Gnomad4 AMR

AF:

0.00699

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00476

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00185

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00552

Hom.:

Bravo

AF:

0.0106

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.00278

EpiControl

AF:

0.00308

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

6.3

DANN

Benign

0.70

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.8

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