Variant 4-100479986-T-C 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_016242.4(EMCN):c.118A>G(p.Ile40Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000448 in 1,605,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

EMCN
NM_016242.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.958

Variant links:

Genes affected

EMCN (HGNC:16041): (endomucin) EMCN is a mucin-like sialoglycoprotein that interferes with the assembly of focal adhesion complexes and inhibits interaction between cells and the extracellular matrix (Kinoshita et al., 2001 [PubMed 11418125]).[supplied by OMIM, Mar 2008]

EMCN links:

LOC124900740 (HGNC:):

LOC124900740 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=0.011249989).

BP6

Variant 4-100479986-T-C is Benign according to our data. Variant chr4-100479986-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2342813.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMCN	NM_016242.4 linkuse as main transcript	c.118A>G	p.Ile40Val	missense_variant	2/12	ENST00000296420.9
LOC124900740	XR_007058203.1 linkuse as main transcript	n.69-31147T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMCN	ENST00000296420.9 linkuse as main transcript	c.118A>G	p.Ile40Val	missense_variant	2/12	1	NM_016242.4	P1	Q9ULC0-1

Frequencies

GnomAD3 genomes

AF:

0.000259

AC:

AN:

146908

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000950

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000826

AC:

AN:

242068

Hom.:

AF XY:

0.0000458

AC XY:

AN XY:

131134

show subpopulations

Gnomad AFR exome

AF:

0.00101

Gnomad AMR exome

AF:

0.0000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000693

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000892

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1458716

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

725602

show subpopulations

Gnomad4 AFR exome

AF:

0.000630

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.000258

AC:

AN:

147022

Hom.:

Cov.:

AF XY:

0.000279

AC XY:

AN XY:

71598

show subpopulations

Gnomad4 AFR

AF:

0.000947

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000225

Hom.:

Bravo

AF:

0.000242

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000132

AC:

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

Jul 14, 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

0.056

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.77

Cadd

Benign

0.0080

Dann

Benign

0.19

DEOGEN2

Benign

0.00046

T;.;.;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.00097

LIST_S2

Benign

0.41

T;T;T;T

M_CAP

Benign

0.00083

MetaRNN

Benign

0.011

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

N;N;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.19

PROVEAN

Benign

0.51

N;N;N;N

REVEL

Benign

0.024

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

0.81

T;T;T;T

Polyphen

0.0

B;B;.;.

Vest4

0.039

MVP

0.030

MPC

0.0093

ClinPred

0.0053

GERP RS

-3.8

Varity_R

0.010

gMVP

0.13

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