Variant 4-70335082-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000273936.6(CABS1):c.43A>G(p.Thr15Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 1,613,462 control chromosomes in the GnomAD database, including 138 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 68 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 70 hom. )

Consequence

CABS1
ENST00000273936.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.02

Variant links:

Genes affected

CABS1 (HGNC:30710): (calcium binding protein, spermatid associated 1) Predicted to enable calcium ion binding activity. Predicted to be involved in flagellated sperm motility and spermatogenesis. Predicted to be located in acrosomal vesicle and sperm principal piece. Predicted to be active in mitochondrial inner membrane and motile cilium. [provided by Alliance of Genome Resources, Apr 2022]

CABS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003003329).

BP6

Variant 4-70335082-A-G is Benign according to our data. Variant chr4-70335082-A-G is described in ClinVar as [Benign]. Clinvar id is 791441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CABS1	NM_033122.4 linkuse as main transcript	c.43A>G	p.Thr15Ala	missense_variant	1/2	ENST00000273936.6	NP_149113.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CABS1	ENST00000273936.6 linkuse as main transcript	c.43A>G	p.Thr15Ala	missense_variant	1/2	1	NM_033122.4	ENSP00000273936	P1

Frequencies

GnomAD3 genomes

AF:

0.0162

AC:

2460

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0539

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00807

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00502

AC:

1250

AN:

249142

Hom.:

AF XY:

0.00394

AC XY:

531

AN XY:

134790

show subpopulations

Gnomad AFR exome

AF:

0.0573

Gnomad AMR exome

AF:

0.00349

Gnomad ASJ exome

AF:

0.0112

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000983

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000570

Gnomad OTH exome

AF:

0.00446

GnomAD4 exome

AF:

0.00218

AC:

3180

AN:

1461292

Hom.:

Cov.:

AF XY:

0.00205

AC XY:

1487

AN XY:

726960

show subpopulations

Gnomad4 AFR exome

AF:

0.0594

Gnomad4 AMR exome

AF:

0.00423

Gnomad4 ASJ exome

AF:

0.0100

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000312

Gnomad4 OTH exome

AF:

0.00552

GnomAD4 genome

AF:

0.0163

AC:

2479

AN:

152170

Hom.:

Cov.:

AF XY:

0.0155

AC XY:

1155

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0542

Gnomad4 AMR

AF:

0.00806

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00382

Hom.:

Bravo

AF:

0.0192

ESP6500AA

AF:

0.0549

AC:

242

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00581

AC:

705

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.000764

EpiControl

AF:

0.000711

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	Oct 19, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.0043

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.35

MetaRNN

Benign

0.0030

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

MutationTaster

Benign

1.0

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.052

Sift

Benign

0.21

Sift4G

Benign

0.61

Polyphen

0.093

Vest4

0.057

MVP

0.10

MPC

0.26

ClinPred

0.023

GERP RS

0.85

Varity_R

0.071

gMVP

0.017

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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