rs719674

Variant names:

• chr8-36903466-C-T
• rs719674
• NM_001031836.3:c.2010-2242C>T

Variant summary

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

The NM_001031836.3(KCNU1):​c.2010-2242C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,992 control chromosomes in the GnomAD database, including 9,682 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 0.34 (9682 hom., cov: 32)
• Consequence: KCNU1 NM_001031836.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• Publications: 1 publications found

Genes affected

KCNU1 (HGNC:18867): (potassium calcium-activated channel subfamily U member 1) This gene encodes a member of the potassium channel family of proteins. The encoded voltage-gated ion channel allows the outward flow of potassium ions during plasma membrane hyperpolarization in sperm. Opening of this channel may be regulated by calcium ion levels. Homozygous knockout mice that lack the related mouse gene exhibit male sterility. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

KCNU1 Gene-Disease associations (from GenCC):

• spermatogenic failure 79

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000302634 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNU1	NM_001031836.3	c.2010-2242C>T		intron_variant	Intron 19 of 26	ENST00000399881.8	NP_001027006.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNU1	ENST00000399881.8	c.2010-2242C>T		intron_variant	Intron 19 of 26	2	NM_001031836.3	ENSP00000382770.3
KCNU1	ENST00000522372.5	n.2010-2242C>T		intron_variant	Intron 19 of 27	1		ENSP00000428552.1
ENSG00000302634	ENST00000788288.1	n.245-3152G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52311 AN: 151874 Hom.: 9678 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.344 AC: 52316 AN: 151992 Hom.: 9682 Cov.: 32 AF XY: 0.343 AC XY: 25511 AN XY: 74282

African (AFR) AF: 0.201 AC: 8318 AN: 41484

American (AMR) AF: 0.419 AC: 6394 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1159 AN: 3470

East Asian (EAS) AF: 0.353 AC: 1818 AN: 5154

South Asian (SAS) AF: 0.344 AC: 1657 AN: 4820

European-Finnish (FIN) AF: 0.379 AC: 3995 AN: 10550

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27724 AN: 67938

Other (OTH) AF: 0.367 AC: 776 AN: 2116

Alfa AF: 0.360 Hom.: 1326

Bravo AF: 0.346

Asia WGS AF: 0.398 AC: 1383 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.6
DANN	Benign	0.40
PhyloP100		-0.086
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: rs719674; hg19: chr8-36760984;