12-110687264-C-A

Variant names:

• chr12-110687264-C-A
• rs7132423
• NM_032369.4:c.-20+1361G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032369.4(HVCN1):​c.-20+1361G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 149,660 control chromosomes in the GnomAD database, including 1 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 0.0014 (1 hom., cov: 30)
• Consequence: HVCN1 NM_032369.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 1 publications found

Genes affected

HVCN1 (HGNC:28240): (hydrogen voltage gated channel 1) This gene encodes a voltage-gated protein channel protein expressed more highly in certain cells of the immune system. Phagocytic cells produce superoxide anions which require this channel protein, and in B cells this same process facilitates antibody production. This same channel protein, however, can also regulate functions in other cells including spermatozoa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HVCN1	NM_032369.4	c.-20+1361G>T		intron_variant	Intron 2 of 7	ENST00000242607.13	NP_115745.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HVCN1	ENST00000242607.13	c.-20+1361G>T		intron_variant	Intron 2 of 7	1	NM_032369.4	ENSP00000242607.8

Frequencies

GnomAD3 genomes AF: 0.00136 AC: 203 AN: 149574 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.00370

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00192

Gnomad ASJ AF: 0.00146

Gnomad EAS AF: 0.000587

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000165

Gnomad OTH AF: 0.00246

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

GnomAD4 genome AF: 0.00136 AC: 204 AN: 149660 Hom.: 1 Cov.: 30 AF XY: 0.00131 AC XY: 96 AN XY: 73010

African (AFR) AF: 0.00372 AC: 151 AN: 40594

American (AMR) AF: 0.00191 AC: 29 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.00146 AC: 5 AN: 3418

East Asian (EAS) AF: 0.000589 AC: 3 AN: 5096

South Asian (SAS) AF: 0.00 AC: 0 AN: 4728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.000165 AC: 11 AN: 66844

Other (OTH) AF: 0.00244 AC: 5 AN: 2048

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.41
PhyloP100		0.055
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7132423; hg19: chr12-111125069;