3-195752385-T-C

Position:

• chr3-195752385-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_018406.7(MUC4):​c.15570A>G​(p.Glu5190=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 1,613,408 control chromosomes in the GnomAD database, including 648,960 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 0.84 (54686 hom., cov: 34)
  • Exomes 𝑓: 0.90 (594274 hom.)
• Consequence: MUC4 NM_018406.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

Genes affected

MUC4 (HGNC:7514): (mucin 4, cell surface associated) The major constituents of mucus, the viscous secretion that covers epithelial surfaces such as those in the trachea, colon, and cervix, are highly glycosylated proteins called mucins. These glycoproteins play important roles in the protection of the epithelial cells and have been implicated in epithelial renewal and differentiation. This gene encodes an integral membrane glycoprotein found on the cell surface, although secreted isoforms may exist. At least two dozen transcript variants of this gene have been found, although for many of them the full-length transcript has not been determined or they are found only in tumor tissues. This gene contains a region in the coding sequence which has a variable number (>100) of 48 nt tandem repeats. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP7: Synonymous conserved (PhyloP=-1.39 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC4	NM_018406.7	c.15570A>G	p.Glu5190=	synonymous_variant	21/25	ENST00000463781.8
MUC4	NM_004532.6	c.2862A>G	p.Glu954=	synonymous_variant	20/24
MUC4	NM_138297.5	c.2709A>G	p.Glu903=	synonymous_variant	19/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC4	ENST00000463781.8	c.15570A>G	p.Glu5190=	synonymous_variant	21/25	5	NM_018406.7	A2

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127943 AN: 152148 Hom.: 54646 Cov.: 34

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.896

Gnomad AMR AF: 0.916

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.878

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.884

GnomAD3 exomes AF: 0.886 AC: 222748 AN: 251454 Hom.: 99369 AF XY: 0.887 AC XY: 120499 AN XY: 135904

Gnomad AFR exome AF: 0.669

Gnomad AMR exome AF: 0.956

Gnomad ASJ exome AF: 0.934

Gnomad EAS exome AF: 0.813

Gnomad SAS exome AF: 0.830

Gnomad FIN exome AF: 0.878

Gnomad NFE exome AF: 0.919

Gnomad OTH exome AF: 0.901

GnomAD4 exome AF: 0.901 AC: 1315814 AN: 1461142 Hom.: 594274 Cov.: 55 AF XY: 0.900 AC XY: 653981 AN XY: 726932

Gnomad4 AFR exome AF: 0.666

Gnomad4 AMR exome AF: 0.952

Gnomad4 ASJ exome AF: 0.939

Gnomad4 EAS exome AF: 0.821

Gnomad4 SAS exome AF: 0.834

Gnomad4 FIN exome AF: 0.880

Gnomad4 NFE exome AF: 0.914

Gnomad4 OTH exome AF: 0.891

GnomAD4 genome AF: 0.841 AC: 128034 AN: 152266 Hom.: 54686 Cov.: 34 AF XY: 0.842 AC XY: 62682 AN XY: 74448

Gnomad4 AFR AF: 0.676

Gnomad4 AMR AF: 0.916

Gnomad4 ASJ AF: 0.937

Gnomad4 EAS AF: 0.811

Gnomad4 SAS AF: 0.830

Gnomad4 FIN AF: 0.878

Gnomad4 NFE AF: 0.914

Gnomad4 OTH AF: 0.885

Alfa AF: 0.904 Hom.: 100417

Bravo AF: 0.837

Asia WGS AF: 0.859 AC: 2987 AN: 3478

EpiCase AF: 0.919

EpiControl AF: 0.923

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.23
DANN	Benign	0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2258447; hg19: chr3-195479256; COSMIC: COSV57794598;