Genetic Variant NM_016242.4:c.313G>A (chr4-100465486-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V105L) has been classified as Uncertain significance.

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

Publications

6 publications found

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:

ENSG00000286150 (HGNC:):

ENSG00000286150 links:

ENSG00000294250 (HGNC:58859):

ENSG00000294250 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016242.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMCN	NM_016242.4	MANE Select	c.313G>A	p.Val105Ile	missense	Exon 4 of 12	NP_057326.2
	EMCN	NM_001159694.2		c.313G>A	p.Val105Ile	missense	Exon 4 of 11	NP_001153166.1	Q9ULC0-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EMCN	ENST00000296420.9	TSL:1 MANE Select	c.313G>A	p.Val105Ile	missense	Exon 4 of 12	ENSP00000296420.4	Q9ULC0-1
EMCN	ENST00000305864.7	TSL:1	c.313G>A	p.Val105Ile	missense	Exon 4 of 9	ENSP00000304780.3	Q9ULC0-2
EMCN	ENST00000956441.1		c.313G>A	p.Val105Ile	missense	Exon 4 of 13	ENSP00000626500.1

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

GnomAD2 exomes

AF:

0.00620

AC:

1546

AN:

249516

AF XY:

0.00518

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 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

African (AFR)

AF:

0.0573

AC:

1905

AN:

33260

American (AMR)

AF:

0.00346

AC:

153

AN:

44278

Ashkenazi Jewish (ASJ)

AF:

0.00100

AC:

AN:

25982

East Asian (EAS)

AF:

0.000759

AC:

AN:

39522

South Asian (SAS)

AF:

0.00300

AC:

256

AN:

85468

European-Finnish (FIN)

AF:

0.00211

AC:

112

AN:

53192

Middle Eastern (MID)

AF:

0.00487

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.00282

AC:

3122

AN:

1108208

Other (OTH)

AF:

0.00577

AC:

347

AN:

60088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

248

496

745

993

1241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

154

308

462

616

770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0178

AC:

2705

AN:

152172

Hom.:

Cov.:

AF XY:

0.0171

AC XY:

1269

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.0564

AC:

2342

AN:

41520

American (AMR)

AF:

0.00851

AC:

130

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3470

East Asian (EAS)

AF:

0.00154

AC:

AN:

5184

South Asian (SAS)

AF:

0.00249

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00142

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00238

AC:

162

AN:

67996

Other (OTH)

AF:

0.0152

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

130

260

389

519

649

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00801

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.014

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.0027

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0027

LIST_S2

Benign

0.33

MetaRNN

Benign

0.0029

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PhyloP100

-2.7

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.57

REVEL

Benign

0.030

Sift

Benign

0.49

Sift4G

Benign

0.39

Polyphen

0.13

Vest4

0.077

MVP

0.014

MPC

0.010

ClinPred

0.0025

GERP RS

-5.4

Varity_R

0.012

gMVP

0.092

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over