14-91620369-A-G

Variant names:

• chr14-91620369-A-G
• rs1298989
• NM_024764.4:c.2260+1239T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024764.4(CATSPERB):​c.2260+1239T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 151,924 control chromosomes in the GnomAD database, including 42,545 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.74 (42545 hom., cov: 29)
• Consequence: CATSPERB NM_024764.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251
• Publications: 4 publications found

Genes affected

CATSPERB (HGNC:20500): (cation channel sperm associated auxiliary subunit beta) Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be located in plasma membrane. Predicted to be part of CatSper complex. Predicted to be active in cilium. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CATSPERB	NM_024764.4	c.2260+1239T>C		intron_variant	Intron 19 of 26	ENST00000256343.8	NP_079040.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CATSPERB	ENST00000256343.8	c.2260+1239T>C		intron_variant	Intron 19 of 26	1	NM_024764.4	ENSP00000256343.3
CATSPERB	ENST00000557036.1	n.*741+1239T>C		intron_variant	Intron 5 of 12	2		ENSP00000451083.1

Frequencies

GnomAD3 genomes AF: 0.744 AC: 112895 AN: 151806 Hom.: 42526 Cov.: 29

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.759

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.744 AC: 112960 AN: 151924 Hom.: 42545 Cov.: 29 AF XY: 0.753 AC XY: 55906 AN XY: 74264

African (AFR) AF: 0.642 AC: 26564 AN: 41380

American (AMR) AF: 0.820 AC: 12527 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2519 AN: 3470

East Asian (EAS) AF: 0.973 AC: 4991 AN: 5132

South Asian (SAS) AF: 0.864 AC: 4157 AN: 4814

European-Finnish (FIN) AF: 0.830 AC: 8776 AN: 10570

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.750 AC: 50947 AN: 67962

Other (OTH) AF: 0.755 AC: 1591 AN: 2108

Alfa AF: 0.754 Hom.: 34172

Bravo AF: 0.738

Asia WGS AF: 0.893 AC: 3107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.3
DANN	Benign	0.66
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1298989; hg19: chr14-92086713;