Genetic Variant CABS1:p.Trp298Gly (chr4-70335931-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033122.4(CABS1):c.892T>G(p.Trp298Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0974 in 1,613,402 control chromosomes in the GnomAD database, including 9,355 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.085 ( 808 hom., cov: 32)

Exomes 𝑓: 0.099 ( 8547 hom. )

Consequence

CABS1
NM_033122.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.31

Publications

16 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019220412).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CABS1	NM_033122.4 link	c.892T>G	p.Trp298Gly	missense_variant	Exon 1 of 2	ENST00000273936.6	NP_149113.3	Q96KC9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CABS1	ENST00000273936.6 link	c.892T>G	p.Trp298Gly	missense_variant	Exon 1 of 2	1	NM_033122.4	ENSP00000273936.4		Q96KC9

Frequencies

GnomAD3 genomes

AF:

0.0852

AC:

12944

AN:

151854

Hom.:

807

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0222

Gnomad AMI

AF:

0.162

Gnomad AMR

AF:

0.0842

Gnomad ASJ

AF:

0.182

Gnomad EAS

AF:

0.198

Gnomad SAS

AF:

0.198

Gnomad FIN

AF:

0.174

Gnomad MID

AF:

0.159

Gnomad NFE

AF:

0.0869

Gnomad OTH

AF:

0.0944

GnomAD2 exomes

AF:

0.114

AC:

28706

AN:

250912

AF XY:

0.121

show subpopulations

Gnomad AFR exome

AF:

0.0213

Gnomad AMR exome

AF:

0.0567

Gnomad ASJ exome

AF:

0.162

Gnomad EAS exome

AF:

0.199

Gnomad FIN exome

AF:

0.175

Gnomad NFE exome

AF:

0.0934

Gnomad OTH exome

AF:

0.121

GnomAD4 exome

AF:

0.0987

AC:

144260

AN:

1461428

Hom.:

8547

Cov.:

AF XY:

0.102

AC XY:

74040

AN XY:

727024

show subpopulations

African (AFR)

AF:

0.0217

AC:

726

AN:

33456

American (AMR)

AF:

0.0585

AC:

2614

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

4377

AN:

26114

East Asian (EAS)

AF:

0.200

AC:

7934

AN:

39676

South Asian (SAS)

AF:

0.195

AC:

16782

AN:

86246

European-Finnish (FIN)

AF:

0.172

AC:

9191

AN:

53380

Middle Eastern (MID)

AF:

0.187

AC:

1077

AN:

5762

European-Non Finnish (NFE)

AF:

0.0854

AC:

94987

AN:

1111714

Other (OTH)

AF:

0.109

AC:

6572

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

7897

15794

23690

31587

39484

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3612

7224

10836

14448

18060

<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:

0.0852

AC:

12948

AN:

151974

Hom.:

808

Cov.:

AF XY:

0.0921

AC XY:

6843

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.0223

AC:

925

AN:

41494

American (AMR)

AF:

0.0841

AC:

1282

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.182

AC:

631

AN:

3462

East Asian (EAS)

AF:

0.198

AC:

1019

AN:

5136

South Asian (SAS)

AF:

0.197

AC:

947

AN:

4816

European-Finnish (FIN)

AF:

0.174

AC:

1843

AN:

10578

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0869

AC:

5903

AN:

67932

Other (OTH)

AF:

0.0958

AC:

202

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

607

1215

1822

2430

3037

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

158

316

474

632

790

<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:

0.0904

Hom.:

2556

Bravo

AF:

0.0738

TwinsUK

AF:

0.0901

AC:

334

ALSPAC

AF:

0.0872

AC:

336

ESP6500AA

AF:

0.0241

AC:

106

ESP6500EA

AF:

0.0885

AC:

761

ExAC

AF:

0.113

AC:

13770

Asia WGS

AF:

0.184

AC:

640

AN:

3476

EpiCase

AF:

0.0975

EpiControl

AF:

0.0994

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.054

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.32

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PhyloP100

3.3

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-12

REVEL

Benign

0.22

Sift

Benign

0.048

Sift4G

Benign

0.36

Polyphen

1.0

Vest4

0.31

MPC

0.36

ClinPred

0.054

GERP RS

4.8

Varity_R

0.29

gMVP

0.0091

Mutation Taster

=90/10

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

Computational scores

Splicing

Publications

Other links and lift over