rs41306094

Variant names:

• chr9-2729733-T-C
• rs41306094
• NM_133497.4:c.*6T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-2729733-T-C
• chr9-2729733-T-G

Variant summary

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

The NM_133497.4(KCNV2):​c.*6T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.077 in 1,612,442 control chromosomes in the GnomAD database, including 5,597 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (963 hom., cov: 32)
  • Exomes 𝑓: 0.075 (4634 hom.)
• Consequence: KCNV2 NM_133497.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.423
• Publications: 5 publications found

Genes affected

KCNV2 (HGNC:19698): (potassium voltage-gated channel modifier subfamily V member 2) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium voltage-gated channel subfamily V. This member is identified as a 'silent subunit', and it does not form homomultimers, but forms heteromultimers with several other subfamily members. Through obligatory heteromerization, it exerts a function-altering effect on other potassium channel subunits. This protein is strongly expressed in pancreas and has a weaker expression in several other tissues. [provided by RefSeq, Jul 2008]

PUM3 (HGNC:29676): (pumilio RNA binding family member 3) Enables RNA binding activity. Involved in regulation of protein ADP-ribosylation. Located in chromosome; endoplasmic reticulum; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286670 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-2729733-T-C is Benign according to our data. Variant chr9-2729733-T-C is described in ClinVar as Benign. ClinVar VariationId is 262358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNV2	NM_133497.4	c.*6T>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000382082.4	NP_598004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNV2	ENST00000382082.4	c.*6T>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_133497.4	ENSP00000371514.3

Frequencies

GnomAD3 genomes AF: 0.0999 AC: 15197 AN: 152074 Hom.: 950 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.0243

Gnomad SAS AF: 0.0475

Gnomad FIN AF: 0.0704

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0745

Gnomad OTH AF: 0.0891

GnomAD2 exomes AF: 0.0842 AC: 21104 AN: 250632 AF XY: 0.0779

Gnomad AFR exome AF: 0.163

Gnomad AMR exome AF: 0.149

Gnomad ASJ exome AF: 0.108

Gnomad EAS exome AF: 0.0242

Gnomad FIN exome AF: 0.0742

Gnomad NFE exome AF: 0.0728

Gnomad OTH exome AF: 0.0786

GnomAD4 exome AF: 0.0745 AC: 108850 AN: 1460250 Hom.: 4634 Cov.: 31 AF XY: 0.0728 AC XY: 52896 AN XY: 726580

African (AFR) AF: 0.163 AC: 5423 AN: 33344

American (AMR) AF: 0.144 AC: 6418 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 2745 AN: 26124

East Asian (EAS) AF: 0.0215 AC: 854 AN: 39690

South Asian (SAS) AF: 0.0469 AC: 4042 AN: 86234

European-Finnish (FIN) AF: 0.0768 AC: 4101 AN: 53402

Middle Eastern (MID) AF: 0.0342 AC: 197 AN: 5762

European-Non Finnish (NFE) AF: 0.0724 AC: 80416 AN: 1110626

Other (OTH) AF: 0.0771 AC: 4654 AN: 60346

GnomAD4 genome AF: 0.100 AC: 15245 AN: 152192 Hom.: 963 Cov.: 32 AF XY: 0.0987 AC XY: 7345 AN XY: 74398

African (AFR) AF: 0.162 AC: 6727 AN: 41522

American (AMR) AF: 0.112 AC: 1706 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 381 AN: 3470

East Asian (EAS) AF: 0.0242 AC: 125 AN: 5170

South Asian (SAS) AF: 0.0473 AC: 228 AN: 4820

European-Finnish (FIN) AF: 0.0704 AC: 746 AN: 10592

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0745 AC: 5066 AN: 68020

Other (OTH) AF: 0.0867 AC: 183 AN: 2110

Alfa AF: 0.0828 Hom.: 509

Bravo AF: 0.107

Asia WGS AF: 0.0510 AC: 176 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Cone dystrophy with supernormal rod response Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.97
DANN	Benign	0.56
PhyloP100		-0.42
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: rs41306094; hg19: chr9-2729733;