4-100462475-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016242.4(EMCN):c.376+2948A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 152,098 control chromosomes in the GnomAD database, including 52,309 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.82 (52309 hom., cov: 32)
• Consequence: EMCN NM_016242.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMCN	NM_016242.4	c.376+2948A>G		intron_variant		ENST00000296420.9
LOC124900740	XR_007058203.1	n.68+41037T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMCN	ENST00000296420.9	c.376+2948A>G		intron_variant		1	NM_016242.4	P1
	ENST00000652064.1	n.309-10959T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124385 AN: 151980 Hom.: 52290 Cov.: 32

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.877

Gnomad ASJ AF: 0.903

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.956

Gnomad FIN AF: 0.933

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.897

Gnomad OTH AF: 0.848

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.818 AC: 124441 AN: 152098 Hom.: 52309 Cov.: 32 AF XY: 0.824 AC XY: 61268 AN XY: 74370

Gnomad4 AFR AF: 0.600

Gnomad4 AMR AF: 0.877

Gnomad4 ASJ AF: 0.903

Gnomad4 EAS AF: 0.917

Gnomad4 SAS AF: 0.957

Gnomad4 FIN AF: 0.933

Gnomad4 NFE AF: 0.897

Gnomad4 OTH AF: 0.847

Alfa AF: 0.816 Hom.: 8522

Bravo AF: 0.801

Asia WGS AF: 0.914 AC: 3179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	2.1
Dann	Benign	0.80

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

Other links and lift over

dbSNP: rs357654; hg19: chr4-101383632;