Variant 2-127631287-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001393586.1(MYO7B):c.5019G>C(p.Glu1673Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,611,760 control chromosomes in the GnomAD database, including 31,852 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.16 ( 2255 hom., cov: 34)

Exomes 𝑓: 0.20 ( 29597 hom. )

Consequence

MYO7B
NM_001393586.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.24

Variant links:

Genes affected

MYO7B (HGNC:7607): (myosin VIIB) The protein encoded by this gene is found in brush border microvilli of epithelial cells in the intestines and kidneys. The encoded protein is involved in linking protocadherins to the actin cytoskeleton and is essential for proper microvilli function. This protein aids in the accumulation of intermicrovillar adhesion components such as harmonin and ANKS4B, and this accumulation is necessary for normal brush border action. [provided by RefSeq, Jan 2017]

MYO7B links:

MYO7B (HGNC:):

MYO7B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024333298).

BP6

Variant 2-127631287-G-C is Benign according to our data. Variant chr2-127631287-G-C is described in ClinVar as [Benign]. Clinvar id is 3055551.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO7B	NM_001393586.1 linkuse as main transcript	c.5019G>C	p.Glu1673Asp	missense_variant	37/48	ENST00000409816.8	NP_001380515.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO7B	ENST00000409816.8 linkuse as main transcript	c.5019G>C	p.Glu1673Asp	missense_variant	37/48	1	NM_001393586.1	ENSP00000386461.3		A0A8C8KL71

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24208

AN:

152162

Hom.:

2255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0672

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.145

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.325

Gnomad FIN

AF:

0.226

Gnomad MID

AF:

0.166

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.168

GnomAD3 exomes

AF:

0.190

AC:

46773

AN:

246006

Hom.:

5089

AF XY:

0.203

AC XY:

27226

AN XY:

134188

show subpopulations

Gnomad AFR exome

AF:

0.0639

Gnomad AMR exome

AF:

0.106

Gnomad ASJ exome

AF:

0.149

Gnomad EAS exome

AF:

0.149

Gnomad SAS exome

AF:

0.318

Gnomad FIN exome

AF:

0.228

Gnomad NFE exome

AF:

0.202

Gnomad OTH exome

AF:

0.187

GnomAD4 exome

AF:

0.196

AC:

286109

AN:

1459480

Hom.:

29597

Cov.:

AF XY:

0.200

AC XY:

145424

AN XY:

725908

show subpopulations

Gnomad4 AFR exome

AF:

0.0629

Gnomad4 AMR exome

AF:

0.112

Gnomad4 ASJ exome

AF:

0.145

Gnomad4 EAS exome

AF:

0.134

Gnomad4 SAS exome

AF:

0.314

Gnomad4 FIN exome

AF:

0.221

Gnomad4 NFE exome

AF:

0.197

Gnomad4 OTH exome

AF:

0.186

GnomAD4 genome

AF:

0.159

AC:

24210

AN:

152280

Hom.:

2255

Cov.:

AF XY:

0.163

AC XY:

12119

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0671

Gnomad4 AMR

AF:

0.145

Gnomad4 ASJ

AF:

0.141

Gnomad4 EAS

AF:

0.139

Gnomad4 SAS

AF:

0.323

Gnomad4 FIN

AF:

0.226

Gnomad4 NFE

AF:

0.200

Gnomad4 OTH

AF:

0.173

Alfa

AF:

0.159

Hom.:

765

Bravo

AF:

0.143

TwinsUK

AF:

0.192

AC:

712

ALSPAC

AF:

0.191

AC:

735

ESP6500AA

AF:

0.0755

AC:

318

ESP6500EA

AF:

0.189

AC:

1605

ExAC

AF:

0.192

AC:

23227

Asia WGS

AF:

0.261

AC:

904

AN:

3476

EpiCase

AF:

0.202

EpiControl

AF:

0.211

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MYO7B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

T;T;T

Eigen

Benign

0.053

Eigen_PC

Benign

0.085

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.83

T;.;T

MetaRNN

Benign

0.0024

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;M;.

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.4

N;N;N

REVEL

Benign

0.17

Sift

Benign

0.20

T;T;T

Sift4G

Benign

0.086

T;T;T

Polyphen

0.85

P;P;.

Vest4

0.36

MutPred

0.25

Loss of phosphorylation at Y1644 (P = 0.1769);Loss of phosphorylation at Y1644 (P = 0.1769);.;

MPC

0.28

ClinPred

0.023

GERP RS

4.9

Varity_R

0.27

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

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

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