4-70335082-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_033122.4(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 NM_033122.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.02

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
CABS1	NM_033122.4	c.43A>G	p.Thr15Ala	missense_variant	1/2	ENST00000273936.6

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0162 AC: 2460 AN: 152052 Hom.: 65 Cov.: 32

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.: 18 AF XY: 0.00394 AC XY: 531 AN XY: 134790

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.: 70 Cov.: 30 AF XY: 0.00205 AC XY: 1487 AN XY: 726960

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.: 68 Cov.: 32 AF XY: 0.0155 AC XY: 1155 AN XY: 74420

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.: 19

Bravo AF: 0.0192

ESP6500AA AF: 0.0549 AC: 242

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.00581 AC: 705

Asia WGS AF: 0.00722 AC: 25 AN: 3478

EpiCase AF: 0.000764

EpiControl AF: 0.000711

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 19, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.73
Cadd	Benign	13
Dann	Benign	0.80
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.052
Sift	Benign	0.21	T
Sift4G	Benign	0.61	T
Polyphen		0.093	B
Vest4		0.057
MVP		0.10
MPC		0.26
ClinPred		0.023	T
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

Other links and lift over

dbSNP: rs115130040; hg19: chr4-71200799;