11-7691240-C-T

Variant names:

• chr11-7691240-C-T
• rs4509745
• NM_198185.7:c.1639+29G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3 BA1

The NM_198185.7(OVCH2):​c.1639+29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 1,573,480 control chromosomes in the GnomAD database, including 293,466 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.52 (22384 hom., cov: 31)
  • Exomes 𝑓: 0.61 (271082 hom.)
• Consequence: OVCH2 NM_198185.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100
• Publications: 24 publications found

Genes affected

OVCH2 (HGNC:29970): (ovochymase 2) Predicted to enable metal ion binding activity and serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be located in extracellular region. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC105376533 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• PP3: BayesDel_noAF computational evidence supports a deleterious effect, 0.27
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OVCH2	NM_198185.7	c.1639+29G>A		intron_variant	Intron 14 of 15	ENST00000533663.6	NP_937828.3
OVCH2	XM_047426878.1	c.1651+29G>A		intron_variant	Intron 14 of 17		XP_047282834.1
LOC105376533	XR_007062576.1	n.166-38C>T		intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OVCH2	ENST00000533663.6	c.1639+29G>A		intron_variant	Intron 14 of 15	5	NM_198185.7	ENSP00000484497.2
OVCH2	ENST00000612000.1	c.1639+29G>A		intron_variant	Intron 14 of 14	5		ENSP00000484790.1
OVCH2	ENST00000673880.1	c.1192+29G>A		intron_variant	Intron 10 of 11			ENSP00000501258.1

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79283 AN: 151840 Hom.: 22386 Cov.: 31

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.733

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.488

GnomAD2 exomes AF: 0.585 AC: 111720 AN: 191112 AF XY: 0.585

Gnomad AFR exome AF: 0.288

Gnomad AMR exome AF: 0.629

Gnomad ASJ exome AF: 0.456

Gnomad EAS exome AF: 0.576

Gnomad FIN exome AF: 0.651

Gnomad NFE exome AF: 0.634

Gnomad OTH exome AF: 0.564

GnomAD4 exome AF: 0.613 AC: 871856 AN: 1421522 Hom.: 271082 Cov.: 37 AF XY: 0.611 AC XY: 429695 AN XY: 703478

African (AFR) AF: 0.286 AC: 9337 AN: 32678

American (AMR) AF: 0.625 AC: 23822 AN: 38102

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 11669 AN: 25400

East Asian (EAS) AF: 0.593 AC: 22395 AN: 37780

South Asian (SAS) AF: 0.510 AC: 41507 AN: 81394

European-Finnish (FIN) AF: 0.653 AC: 33372 AN: 51084

Middle Eastern (MID) AF: 0.442 AC: 2515 AN: 5696

European-Non Finnish (NFE) AF: 0.636 AC: 693780 AN: 1090532

Other (OTH) AF: 0.568 AC: 33459 AN: 58856

GnomAD4 genome AF: 0.522 AC: 79284 AN: 151958 Hom.: 22384 Cov.: 31 AF XY: 0.522 AC XY: 38777 AN XY: 74286

African (AFR) AF: 0.296 AC: 12268 AN: 41432

American (AMR) AF: 0.577 AC: 8807 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1583 AN: 3470

East Asian (EAS) AF: 0.586 AC: 3008 AN: 5132

South Asian (SAS) AF: 0.500 AC: 2411 AN: 4826

European-Finnish (FIN) AF: 0.634 AC: 6686 AN: 10552

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42695 AN: 67956

Other (OTH) AF: 0.486 AC: 1028 AN: 2114

Alfa AF: 0.582 Hom.: 103109

Bravo AF: 0.505

Asia WGS AF: 0.515 AC: 1793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Pathogenic	0.27
CADD	Benign	3.4
DANN	Benign	0.93
PhyloP100		0.0010
Mutation Taster		=189/11	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: rs4509745; hg19: chr11-7712471; COSMIC: COSV71952845;