chr4-100465486-C-T

Variant names:

• chr4-100465486-C-T
• rs78403369
• NM_016242.4:c.313G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.67
• Publications: 6 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]

ENSG00000286150 (HGNC:):

ENSG00000294250 (HGNC:58859):

ACMG classification

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

Sel.	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.: 68 Cov.: 32

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

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.: 81 Cov.: 29 AF XY: 0.00390 AC XY: 2827 AN XY: 724138

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: 26 AN: 25982

East Asian (EAS) AF: 0.000759 AC: 30 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: 28 AN: 5744

European-Non Finnish (NFE) AF: 0.00282 AC: 3122 AN: 1108208

Other (OTH) AF: 0.00577 AC: 347 AN: 60088

GnomAD4 genome AF: 0.0178 AC: 2705 AN: 152172 Hom.: 68 Cov.: 32 AF XY: 0.0171 AC XY: 1269 AN XY: 74386

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: 4 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5184

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4822

European-Finnish (FIN) AF: 0.00142 AC: 15 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00238 AC: 162 AN: 67996

Other (OTH) AF: 0.0152 AC: 32 AN: 2110

Alfa AF: 0.00801 Hom.: 80

Bravo AF: 0.0205

TwinsUK AF: 0.00351 AC: 13

ALSPAC AF: 0.00208 AC: 8

ESP6500AA AF: 0.0581 AC: 256

ESP6500EA AF: 0.00372 AC: 32

ExAC AF: 0.00747 AC: 907

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.69	T
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	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		-2.7
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.030
Sift	Benign	0.49	T
Sift4G	Benign	0.39	T
Polyphen		0.13	B
Vest4		0.077
MVP		0.014
MPC		0.010
ClinPred		0.0025	T
GERP RS		-5.4
Varity_R		0.012
gMVP		0.092
Mutation Taster		=100/0	polymorphism (auto)

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: rs78403369; hg19: chr4-101386643;