chr4-100415922-C-T

Variant names:

• chr4-100415922-C-T
• rs186967769
• NM_016242.4:c.727G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016242.4(EMCN):​c.727G>A​(p.Val243Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000202 in 1,585,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: EMCN NM_016242.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 4.37
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.033173323).

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.727G>A	p.Val243Ile	missense	Exon 10 of 12	NP_057326.2
	EMCN	NM_001159694.2		c.688G>A	p.Val230Ile	missense	Exon 9 of 11	NP_001153166.1	Q9ULC0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMCN	ENST00000296420.9	TSL:1 MANE Select	c.727G>A	p.Val243Ile	missense	Exon 10 of 12	ENSP00000296420.4	Q9ULC0-1
	EMCN	ENST00000305864.7	TSL:1	c.478G>A	p.Val160Ile	missense	Exon 7 of 9	ENSP00000304780.3	Q9ULC0-2
	EMCN	ENST00000956441.1		c.727G>A	p.Val243Ile	missense	Exon 10 of 13	ENSP00000626500.1

Frequencies

GnomAD3 genomes AF: 0.000290 AC: 44 AN: 151466 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000971

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000417

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.000961

GnomAD2 exomes AF: 0.000343 AC: 77 AN: 224288 AF XY: 0.000304

Gnomad AFR exome AF: 0.000139

Gnomad AMR exome AF: 0.000355

Gnomad ASJ exome AF: 0.00488

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000951

Gnomad OTH exome AF: 0.000187

GnomAD4 exome AF: 0.000191 AC: 274 AN: 1433880 Hom.: 0 Cov.: 28 AF XY: 0.000216 AC XY: 154 AN XY: 712862

African (AFR) AF: 0.0000636 AC: 2 AN: 31428

American (AMR) AF: 0.000330 AC: 13 AN: 39336

Ashkenazi Jewish (ASJ) AF: 0.00479 AC: 123 AN: 25668

East Asian (EAS) AF: 0.00 AC: 0 AN: 38030

South Asian (SAS) AF: 0.000299 AC: 24 AN: 80284

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53158

Middle Eastern (MID) AF: 0.00161 AC: 9 AN: 5598

European-Non Finnish (NFE) AF: 0.0000690 AC: 76 AN: 1101080

Other (OTH) AF: 0.000455 AC: 27 AN: 59298

GnomAD4 genome AF: 0.000303 AC: 46 AN: 151576 Hom.: 0 Cov.: 32 AF XY: 0.000257 AC XY: 19 AN XY: 74012

African (AFR) AF: 0.000145 AC: 6 AN: 41322

American (AMR) AF: 0.000197 AC: 3 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.00663 AC: 23 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.000418 AC: 2 AN: 4790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67928

Other (OTH) AF: 0.000951 AC: 2 AN: 2102

Alfa AF: 0.000425 Hom.: 1

Bravo AF: 0.000238

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000264 AC: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	T
Eigen	Uncertain	0.64
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	1.0	L
PhyloP100		4.4
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.70
MVP		0.21
MPC		0.052
ClinPred		0.076	T
GERP RS		5.7
Varity_R		0.37
gMVP		0.56
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs186967769; hg19: chr4-101337079; COSMIC: COSV56458538;