rs190482876

Variant names:

• chr15-43632151-C-T
• rs190482876
• NM_172095.4:c.1561+48G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-43632151-C-T
• chr15-43632151-C-A
• chr15-43632151-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_172095.4(CATSPER2):​c.1561+48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00754 in 144,570 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0075 (19 hom., cov: 32)
  • Exomes 𝑓: 0.025 (20 hom.)
  • Failed GnomAD Quality Control
• Consequence: CATSPER2 NM_172095.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.01
• Publications: 1 publications found

Genes affected

CATSPER2 (HGNC:18810): (cation channel sperm associated 2) This gene encodes a member of a family of cation channel proteins that localize to the flagellum of spermatozoa. Defects at this locus causes male infertility. Alternatively spliced transcript variants have been observed at this locus. Readthrough transcription originates upstream of this locus in diphosphoinositol pentakisphosphate kinase 1 pseudogene 1 and is represented by GeneID:110006325. Related pseudogenes are found next to this locus on chromosome 15 and on chromosome 5. [provided by RefSeq, Mar 2017]

ENSG00000284772 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 15-43632151-C-T is Benign according to our data. Variant chr15-43632151-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1216831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00754 (1090/144570) while in subpopulation AFR AF = 0.0232 (949/40886). AF 95% confidence interval is 0.022. There are 19 homozygotes in GnomAd4. There are 518 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172095.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATSPER2	NM_172095.4	MANE Select	c.1561+48G>A		intron	N/A	NP_742093.1	Q96P56-1
	CATSPER2	NM_001282310.2		c.1573+48G>A		intron	N/A	NP_001269239.1	F8W9H2
	CATSPER2	NM_001282309.3		c.1555+48G>A		intron	N/A	NP_001269238.1	Q96P56-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATSPER2	ENST00000396879.8	TSL:2 MANE Select	c.1561+48G>A		intron	N/A	ENSP00000380088.3	Q96P56-1
	CATSPER2	ENST00000381761.6	TSL:1	c.1573+48G>A		intron	N/A	ENSP00000371180.1	F8W9H2
	CATSPER2	ENST00000433380.5	TSL:1	n.*98+48G>A		intron	N/A	ENSP00000389746.1	Q96P56-3

Frequencies

GnomAD3 genomes AF: 0.00752 AC: 1087 AN: 144456 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.0232

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00337

Gnomad ASJ AF: 0.00220

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00195

Gnomad FIN AF: 0.000399

Gnomad MID AF: 0.0133

Gnomad NFE AF: 0.000886

Gnomad OTH AF: 0.00617

GnomAD2 exomes AF: 0.00382 AC: 896 AN: 234394 AF XY: 0.00326

Gnomad AFR exome AF: 0.0223

Gnomad AMR exome AF: 0.00276

Gnomad ASJ exome AF: 0.00832

Gnomad EAS exome AF: 0.00204

Gnomad FIN exome AF: 0.000930

Gnomad NFE exome AF: 0.00233

Gnomad OTH exome AF: 0.00352

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0248 AC: 29834 AN: 1203422 Hom.: 20 Cov.: 27 AF XY: 0.0230 AC XY: 13898 AN XY: 603004

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0234 AC: 743 AN: 31794

American (AMR) AF: 0.00600 AC: 248 AN: 41314

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 356 AN: 21658

East Asian (EAS) AF: 0.00345 AC: 126 AN: 36560

South Asian (SAS) AF: 0.00701 AC: 540 AN: 76990

European-Finnish (FIN) AF: 0.00260 AC: 124 AN: 47638

Middle Eastern (MID) AF: 0.0188 AC: 88 AN: 4688

European-Non Finnish (NFE) AF: 0.0298 AC: 26610 AN: 891826

Other (OTH) AF: 0.0196 AC: 999 AN: 50954

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00754 AC: 1090 AN: 144570 Hom.: 19 Cov.: 32 AF XY: 0.00734 AC XY: 518 AN XY: 70598

African (AFR) AF: 0.0232 AC: 949 AN: 40886

American (AMR) AF: 0.00336 AC: 49 AN: 14570

Ashkenazi Jewish (ASJ) AF: 0.00220 AC: 7 AN: 3186

East Asian (EAS) AF: 0.00 AC: 0 AN: 4990

South Asian (SAS) AF: 0.00195 AC: 9 AN: 4618

European-Finnish (FIN) AF: 0.000399 AC: 4 AN: 10014

Middle Eastern (MID) AF: 0.0144 AC: 4 AN: 278

European-Non Finnish (NFE) AF: 0.000886 AC: 56 AN: 63200

Other (OTH) AF: 0.00610 AC: 12 AN: 1966

Alfa AF: 0.0190 Hom.: 1

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.077
DANN	Benign	0.55
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs190482876; hg19: chr15-43924349; COSMIC: COSV58661338; COSMIC: COSV58661338;