chr1-111427097-A-G

Position:

• chr1-111427097-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
OVGP1	NM_002557.4	c.26-6T>C		splice_region_variant, intron_variant		ENST00000369732.4	NP_002548.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OVGP1	ENST00000369732.4	c.26-6T>C		splice_region_variant, intron_variant		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

GnomAD3 exomes AF: 0.455 AC: 114245 AN: 250834 Hom.: 28548 AF XY: 0.461 AC XY: 62494 AN XY: 135566

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 SAS exome AF: 0.612

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

Gnomad4 AFR exome AF: 0.678

Gnomad4 AMR exome AF: 0.272

Gnomad4 ASJ exome AF: 0.289

Gnomad4 EAS exome AF: 0.757

Gnomad4 SAS exome AF: 0.611

Gnomad4 FIN exome AF: 0.449

Gnomad4 NFE exome AF: 0.408

Gnomad4 OTH exome AF: 0.440

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

Gnomad4 AFR AF: 0.658

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.743

Gnomad4 SAS AF: 0.616

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.457

Alfa AF: 0.430 Hom.: 11638

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1264894; hg19: chr1-111969719;