Variant chr7-5880948-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001097622.2(OCM):c.59G>A(p.Arg20Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000928 in 1,613,428 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00097 ( 2 hom. )

Consequence

OCM
NM_001097622.2 missense, splice_region

Scores

Splicing: ADA: 0.000006581

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.37

Variant links:

Genes affected

OCM (HGNC:8105): (oncomodulin) Oncomodulin is a high-affinity calcium ion-binding protein. It belongs to the superfamily of calmodulin proteins, also known as the EF-hand proteins. Oncomodulin is an oncodevelopmental protein found in early embryonic cells in the placenta and also in tumors. [provided by RefSeq, Jul 2008]

OCM links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019145578).

BP6

Variant 7-5880948-G-A is Benign according to our data. Variant chr7-5880948-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3203950.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OCM	NM_001097622.2 linkuse as main transcript	c.59G>A	p.Arg20Gln	missense_variant, splice_region_variant	1/4	ENST00000242104.6	NP_001091091.1	P0CE72
OCM	NM_001391990.1 linkuse as main transcript	c.59G>A	p.Arg20Gln	missense_variant, splice_region_variant	2/5		NP_001378919.1
OCM	NM_001391991.1 linkuse as main transcript	c.-53-1545G>A		intron_variant			NP_001378920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OCM	ENST00000242104.6 linkuse as main transcript	c.59G>A	p.Arg20Gln	missense_variant, splice_region_variant	1/4	1	NM_001097622.2	ENSP00000242104.5		P0CE72
OCM	ENST00000416608.5 linkuse as main transcript	c.59G>A	p.Arg20Gln	missense_variant, splice_region_variant	2/5	5		ENSP00000401365.1		P0CE72

Frequencies

GnomAD3 genomes

AF:

0.000526

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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:

0.00104

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000644

AC:

162

AN:

251402

Hom.:

AF XY:

0.000677

AC XY:

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00135

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000970

AC:

1417

AN:

1461348

Hom.:

Cov.:

AF XY:

0.000919

AC XY:

668

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.00124

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.000526

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.000579

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00104

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.000559

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000618

AC:

EpiCase

AF:

0.000873

EpiControl

AF:

0.00119

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

Nov 15, 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

0.065

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.049

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.0067

LIST_S2

Benign

0.24

.;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.019

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-2.3

N;N

PrimateAI

Uncertain

0.65

PROVEAN

Benign

1.2

N;N

REVEL

Benign

0.15

Sift

Benign

0.95

T;T

Sift4G

Benign

0.88

T;T

Polyphen

0.0

B;B

Vest4

0.26

MVP

0.072

MPC

0.035

ClinPred

0.015

GERP RS

2.9

Varity_R

0.034

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000066

dbscSNV1_RF

Benign

0.012

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