Variant 11-65794581-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_004561.4(OVOL1):c.362G>A(p.Arg121His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000252 in 1,613,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

OVOL1
NM_004561.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.21

Variant links:

Genes affected

OVOL1 (HGNC:8525): (ovo like transcriptional repressor 1) This gene encodes a putative zinc finger containing transcription factor that is highly similar to homologous protein in Drosophila and mouse. Based on known functions in these species, this protein is likely involved in hair formation and spermatogenesis in human as well. [provided by RefSeq, Aug 2011]

OVOL1 links:

LOC124902693 (HGNC:):

LOC124902693 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020645827).

BP6

Variant 11-65794581-G-A is Benign according to our data. Variant chr11-65794581-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2366763.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OVOL1	NM_004561.4 linkuse as main transcript	c.362G>A	p.Arg121His	missense_variant	3/4	ENST00000335987.8	NP_004552.2	O14753
LOC124902693	XM_047427980.1 linkuse as main transcript	c.*1162-2194C>T		intron_variant			XP_047283936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OVOL1	ENST00000335987.8 linkuse as main transcript	c.362G>A	p.Arg121His	missense_variant	3/4	1	NM_004561.4	ENSP00000337862.3		O14753
OVOL1	ENST00000532448.1 linkuse as main transcript	c.176G>A	p.Arg59His	missense_variant	2/3	1		ENSP00000434220.1		G3V1B0

Frequencies

GnomAD3 genomes

AF:

0.000328

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000223

AC:

AN:

250986

Hom.:

AF XY:

0.000250

AC XY:

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000335

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000244

AC:

357

AN:

1461136

Hom.:

Cov.:

AF XY:

0.000234

AC XY:

170

AN XY:

726886

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000264

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000328

AC:

AN:

152358

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000367

Hom.:

Bravo

AF:

0.000382

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000247

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000415

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.21

T;.

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.064

T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.021

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.26

N;.

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.14

Sift

Benign

0.40

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.0

B;.

Vest4

0.17

MVP

0.33

MPC

0.72

ClinPred

0.025

GERP RS

3.8

Varity_R

0.044

gMVP

0.22

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over