1-111427097-A-G

Variant names:

• chr1-111427097-A-G
• rs1264894
• NM_002557.4:c.26-6T>C

Variant summary

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

The NM_002557.4(OVGP1):​c.26-6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,613,458 control chromosomes in the GnomAD database, including 162,296 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.49 (19502 hom., cov: 31)
  • Exomes 𝑓: 0.43 (142794 hom.)
• Consequence: OVGP1 NM_002557.4 splice_region, intron
• Scores: Splicing: ADA: 0.00001320
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• Publications: 23 publications found

Genes affected

OVGP1 (HGNC:8524): (oviductal glycoprotein 1) This gene encodes a large, carbohydrate-rich, epithelial glycoprotein with numerous O-glycosylation sites located within threonine, serine, and proline-rich tandem repeats. The gene is similar to members of the mucin and the glycosyl hydrolase 18 gene families. Regulation of expression may be estrogen-dependent. Gene expression and protein secretion occur during late follicular development through early cleavage-stage embryonic development. The protein is secreted from non-ciliated oviductal epithelial cells and associates with ovulated oocytes, blastomeres, and spermatozoan acrosomal regions. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OVGP1	NM_002557.4	c.26-6T>C		splice_region_variant, intron_variant	Intron 1 of 10	ENST00000369732.4	NP_002548.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OVGP1	ENST00000369732.4	c.26-6T>C		splice_region_variant, intron_variant	Intron 1 of 10	1	NM_002557.4	ENSP00000358747.3

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74250 AN: 151782 Hom.: 19473 Cov.: 31

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.459

GnomAD2 exomes AF: 0.455 AC: 114245 AN: 250834 AF XY: 0.461

Gnomad AFR exome AF: 0.667

Gnomad AMR exome AF: 0.267

Gnomad ASJ exome AF: 0.290

Gnomad EAS exome AF: 0.745

Gnomad FIN exome AF: 0.452

Gnomad NFE exome AF: 0.411

Gnomad OTH exome AF: 0.415

GnomAD4 exome AF: 0.432 AC: 631740 AN: 1461558 Hom.: 142794 Cov.: 48 AF XY: 0.437 AC XY: 317732 AN XY: 727072

African (AFR) AF: 0.678 AC: 22693 AN: 33470

American (AMR) AF: 0.272 AC: 12151 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 7560 AN: 26130

East Asian (EAS) AF: 0.757 AC: 30023 AN: 39686

South Asian (SAS) AF: 0.611 AC: 52645 AN: 86226

European-Finnish (FIN) AF: 0.449 AC: 23992 AN: 53410

Middle Eastern (MID) AF: 0.384 AC: 2215 AN: 5768

European-Non Finnish (NFE) AF: 0.408 AC: 453893 AN: 1111792

Other (OTH) AF: 0.440 AC: 26568 AN: 60380

GnomAD4 genome AF: 0.489 AC: 74335 AN: 151900 Hom.: 19502 Cov.: 31 AF XY: 0.494 AC XY: 36673 AN XY: 74238

African (AFR) AF: 0.658 AC: 27256 AN: 41426

American (AMR) AF: 0.336 AC: 5129 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1024 AN: 3464

East Asian (EAS) AF: 0.743 AC: 3824 AN: 5148

South Asian (SAS) AF: 0.616 AC: 2962 AN: 4808

European-Finnish (FIN) AF: 0.450 AC: 4743 AN: 10548

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.413 AC: 28029 AN: 67922

Other (OTH) AF: 0.457 AC: 965 AN: 2112

Alfa AF: 0.431 Hom.: 14586

Bravo AF: 0.483

Asia WGS AF: 0.618 AC: 2151 AN: 3478

EpiCase AF: 0.403

EpiControl AF: 0.394

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.60
PhyloP100		0.036
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000013
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.020		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: rs1264894; hg19: chr1-111969719;