chr1-111415099-C-T

Position:

• chr1-111415099-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002557.4(OVGP1):​c.1402G>A​(p.Gly468Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000784 in 1,614,186 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0040 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (6 hom.)
• Consequence: OVGP1 NM_002557.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.515

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]

LOC124904309 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0031580627).
• BP6: Variant 1-111415099-C-T is Benign according to our data. Variant chr1-111415099-C-T is described in ClinVar as [Benign]. Clinvar id is 783940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000446 (652/1461876) while in subpopulation AFR AF= 0.0173 (578/33480). AF 95% confidence interval is 0.0161. There are 6 homozygotes in gnomad4_exome. There are 273 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OVGP1	NM_002557.4	c.1402G>A	p.Gly468Arg	missense_variant	11/11	ENST00000369732.4
LOC124904309	XR_007066387.1	n.219C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OVGP1	ENST00000369732.4	c.1402G>A	p.Gly468Arg	missense_variant	11/11	1	NM_002557.4	P1

Frequencies

GnomAD3 genomes AF: 0.00402 AC: 612 AN: 152192 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000850

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00101 AC: 255 AN: 251482 Hom.: 0 AF XY: 0.000625 AC XY: 85 AN XY: 135914

Gnomad AFR exome AF: 0.0151

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000446 AC: 652 AN: 1461876 Hom.: 6 Cov.: 33 AF XY: 0.000375 AC XY: 273 AN XY: 727240

Gnomad4 AFR exome AF: 0.0173

Gnomad4 AMR exome AF: 0.000291

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000162

Gnomad4 OTH exome AF: 0.000679

GnomAD4 genome AF: 0.00402 AC: 613 AN: 152310 Hom.: 3 Cov.: 32 AF XY: 0.00364 AC XY: 271 AN XY: 74474

Gnomad4 AFR AF: 0.0142

Gnomad4 AMR AF: 0.000849

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.000766 Hom.: 0

Bravo AF: 0.00488

ESP6500AA AF: 0.0129 AC: 57

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00120 AC: 146

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.58	T
MetaRNN	Benign	0.0032	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.078
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.045	D
Polyphen		0.68	P
Vest4		0.17
MutPred		0.18		Gain of MoRF binding (P = 0.0168);
MVP		0.48
MPC		0.10
ClinPred		0.031	T
GERP RS		-0.95
Varity_R		0.081
gMVP		0.090

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

Publications

LitVar

Other links and lift over

dbSNP: rs115512535; hg19: chr1-111957721;