12-110687264-C-G

Variant names:

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

Variant summary

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

The NM_032369.4(HVCN1):​c.-20+1361G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0246 in 149,658 control chromosomes in the GnomAD database, including 217 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 0.025 (217 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0771 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032369.4. 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
	HVCN1	NM_032369.4	MANE Select	c.-20+1361G>C		intron	N/A	NP_115745.2	Q96D96-1
	HVCN1	NM_001040107.2		c.-20+1361G>C		intron	N/A	NP_001035196.1	Q96D96-1
	HVCN1	NM_001256413.2		c.-40+1361G>C		intron	N/A	NP_001243342.1	Q96D96-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HVCN1	ENST00000242607.13	TSL:1 MANE Select	c.-20+1361G>C		intron	N/A	ENSP00000242607.8	Q96D96-1
	HVCN1	ENST00000356742.9	TSL:1	c.-20+711G>C		intron	N/A	ENSP00000349181.5	Q96D96-1
	HVCN1	ENST00000888560.1		c.-20+1361G>C		intron	N/A	ENSP00000558619.1

Frequencies

GnomAD3 genomes AF: 0.0245 AC: 3667 AN: 149572 Hom.: 218 Cov.: 30

Gnomad AFR AF: 0.0793

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0139

Gnomad ASJ AF: 0.00293

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00987

Gnomad NFE AF: 0.00211

Gnomad OTH AF: 0.0167

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

GnomAD4 genome AF: 0.0246 AC: 3677 AN: 149658 Hom.: 217 Cov.: 30 AF XY: 0.0239 AC XY: 1746 AN XY: 73010

African (AFR) AF: 0.0794 AC: 3222 AN: 40592

American (AMR) AF: 0.0139 AC: 211 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.00293 AC: 10 AN: 3418

East Asian (EAS) AF: 0.00 AC: 0 AN: 5096

South Asian (SAS) AF: 0.0116 AC: 55 AN: 4728

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10596

Middle Eastern (MID) AF: 0.0106 AC: 3 AN: 282

European-Non Finnish (NFE) AF: 0.00211 AC: 141 AN: 66844

Other (OTH) AF: 0.0166 AC: 34 AN: 2048

Alfa AF: 0.000390 Hom.: 1

Bravo AF: 0.0289

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.30
PhyloP100		0.055
Mutation Taster		=100/0	polymorphism (auto)

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;