NM_172095.4:c.1179-8T>C

Variant names:

• chr15-43632942-A-G
• rs7167634
• NM_172095.4:c.1179-8T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_172095.4(CATSPER2):​c.1179-8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 150,662 control chromosomes in the GnomAD database, including 15,163 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (15163 hom., cov: 29)
  • Exomes 𝑓: 0.29 (67559 hom.)
  • Failed GnomAD Quality Control
• Consequence: CATSPER2 NM_172095.4 splice_region, intron
• Scores: Splicing: ADA: 0.00006217
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.12
• Publications: 11 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]

ENSG00000309475 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 15-43632942-A-G is Benign according to our data. Variant chr15-43632942-A-G is described in ClinVar as Benign. ClinVar VariationId is 517821.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

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.1179-8T>C		splice_region intron	N/A	NP_742093.1	Q96P56-1
	CATSPER2	NM_001282310.2		c.1197-14T>C		intron	N/A	NP_001269239.1	F8W9H2
	CATSPER2	NM_001282309.3		c.1179-14T>C		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.1179-8T>C		splice_region intron	N/A	ENSP00000380088.3	Q96P56-1
	CATSPER2	ENST00000381761.6	TSL:1	c.1197-14T>C		intron	N/A	ENSP00000371180.1	F8W9H2
	CATSPER2	ENST00000433380.5	TSL:1	n.1179-579T>C		intron	N/A	ENSP00000389746.1	Q96P56-3

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60067 AN: 150550 Hom.: 15118 Cov.: 29

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.377

GnomAD2 exomes AF: 0.317 AC: 77262 AN: 243608 AF XY: 0.314

Gnomad AFR exome AF: 0.713

Gnomad AMR exome AF: 0.301

Gnomad ASJ exome AF: 0.381

Gnomad EAS exome AF: 0.329

Gnomad FIN exome AF: 0.180

Gnomad NFE exome AF: 0.274

Gnomad OTH exome AF: 0.304

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.291 AC: 415865 AN: 1428744 Hom.: 67559 Cov.: 28 AF XY: 0.293 AC XY: 208533 AN XY: 712108

African (AFR) AF: 0.729 AC: 23488 AN: 32238

American (AMR) AF: 0.305 AC: 13464 AN: 44176

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 9806 AN: 25838

East Asian (EAS) AF: 0.332 AC: 13100 AN: 39456

South Asian (SAS) AF: 0.364 AC: 30872 AN: 84822

European-Finnish (FIN) AF: 0.182 AC: 9564 AN: 52694

Middle Eastern (MID) AF: 0.392 AC: 2221 AN: 5664

European-Non Finnish (NFE) AF: 0.272 AC: 294559 AN: 1084602

Other (OTH) AF: 0.317 AC: 18791 AN: 59254

GnomAD4 genome AF: 0.399 AC: 60163 AN: 150662 Hom.: 15163 Cov.: 29 AF XY: 0.394 AC XY: 28979 AN XY: 73628

African (AFR) AF: 0.711 AC: 28959 AN: 40744

American (AMR) AF: 0.339 AC: 5145 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1279 AN: 3442

East Asian (EAS) AF: 0.324 AC: 1672 AN: 5154

South Asian (SAS) AF: 0.355 AC: 1689 AN: 4754

European-Finnish (FIN) AF: 0.179 AC: 1873 AN: 10492

Middle Eastern (MID) AF: 0.445 AC: 129 AN: 290

European-Non Finnish (NFE) AF: 0.272 AC: 18428 AN: 67628

Other (OTH) AF: 0.378 AC: 791 AN: 2094

Alfa AF: 0.343 Hom.: 1979

Bravo AF: 0.429

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.31
DANN	Benign	0.51
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000062
dbscSNV1_RF	Benign	0.030
SpliceAI score (max)		0.070		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: rs7167634; hg19: chr15-43925140;