Variant 4-100465486-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016242.4(EMCN):c.313G>A(p.Val105Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0054 in 1,607,914 control chromosomes in the GnomAD database, including 149 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 68 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 81 hom. )

Consequence

EMCN
NM_016242.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.67

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028885603).

BP6

Variant 4-100465486-C-T is Benign according to our data. Variant chr4-100465486-C-T is described in ClinVar as [Benign]. Clinvar id is 776002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMCN	NM_016242.4 linkuse as main transcript	c.313G>A	p.Val105Ile	missense_variant	4/12	ENST00000296420.9	NP_057326.2
LOC124900740	XR_007058203.1 linkuse as main transcript	n.68+44048C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMCN	ENST00000296420.9 linkuse as main transcript	c.313G>A	p.Val105Ile	missense_variant	4/12	1	NM_016242.4	ENSP00000296420	P1	Q9ULC0-1
	ENST00000652064.1 linkuse as main transcript	n.309-7948C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0177

AC:

2688

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0562

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00852

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00142

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00238

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.00620

AC:

1546

AN:

249516

Hom.:

AF XY:

0.00518

AC XY:

699

AN XY:

135022

show subpopulations

Gnomad AFR exome

AF:

0.0586

Gnomad AMR exome

AF:

0.00276

Gnomad ASJ exome

AF:

0.000997

Gnomad EAS exome

AF:

0.00230

Gnomad SAS exome

AF:

0.00330

Gnomad FIN exome

AF:

0.00218

Gnomad NFE exome

AF:

0.00257

Gnomad OTH exome

AF:

0.00297

GnomAD4 exome

AF:

0.00411

AC:

5979

AN:

1455742

Hom.:

Cov.:

AF XY:

0.00390

AC XY:

2827

AN XY:

724138

show subpopulations

Gnomad4 AFR exome

AF:

0.0573

Gnomad4 AMR exome

AF:

0.00346

Gnomad4 ASJ exome

AF:

0.00100

Gnomad4 EAS exome

AF:

0.000759

Gnomad4 SAS exome

AF:

0.00300

Gnomad4 FIN exome

AF:

0.00211

Gnomad4 NFE exome

AF:

0.00282

Gnomad4 OTH exome

AF:

0.00577

GnomAD4 genome

AF:

0.0178

AC:

2705

AN:

152172

Hom.:

Cov.:

AF XY:

0.0171

AC XY:

1269

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0564

Gnomad4 AMR

AF:

0.00851

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00142

Gnomad4 NFE

AF:

0.00238

Gnomad4 OTH

AF:

0.0152

Alfa

AF:

0.00506

Hom.:

Bravo

AF:

0.0205

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.0581

AC:

256

ESP6500EA

AF:

0.00372

AC:

ExAC

AF:

0.00747

AC:

907

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Apr 03, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.014

DANN

Benign

0.51

DEOGEN2

Benign

0.0027

T;.;.;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0027

LIST_S2

Benign

0.33

T;T;T;T;T

MetaRNN

Benign

0.0029

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N;.;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.57

N;N;N;N;N

REVEL

Benign

0.030

Sift

Benign

0.49

T;T;T;T;T

Sift4G

Benign

0.39

T;T;T;T;T

Polyphen

0.13

B;B;.;.;.

Vest4

0.077

MVP

0.014

MPC

0.010

ClinPred

0.0025

GERP RS

-5.4

Varity_R

0.012

gMVP

0.092

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