3-195752385-T-C

Variant names:

• chr3-195752385-T-C
• rs2258447
• NM_018406.7:c.15570A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_018406.7(MUC4):​c.15570A>G​(p.Glu5190Glu) 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
• Publications: 31 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MUC4	NM_018406.7	c.15570A>G	p.Glu5190Glu	synonymous_variant	Exon 21 of 25	ENST00000463781.8	NP_060876.5
MUC4	NM_004532.6	c.2862A>G	p.Glu954Glu	synonymous_variant	Exon 20 of 24		NP_004523.3
MUC4	NM_138297.5	c.2709A>G	p.Glu903Glu	synonymous_variant	Exon 19 of 23		NP_612154.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC4	ENST00000463781.8	c.15570A>G	p.Glu5190Glu	synonymous_variant	Exon 21 of 25	5	NM_018406.7	ENSP00000417498.3

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

GnomAD2 exomes AF: 0.886 AC: 222748 AN: 251454 AF XY: 0.887

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 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

African (AFR) AF: 0.666 AC: 22272 AN: 33442

American (AMR) AF: 0.952 AC: 42553 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.939 AC: 24526 AN: 26132

East Asian (EAS) AF: 0.821 AC: 32599 AN: 39692

South Asian (SAS) AF: 0.834 AC: 71891 AN: 86240

European-Finnish (FIN) AF: 0.880 AC: 47014 AN: 53410

Middle Eastern (MID) AF: 0.904 AC: 5217 AN: 5768

European-Non Finnish (NFE) AF: 0.914 AC: 1015961 AN: 1111360

Other (OTH) AF: 0.891 AC: 53781 AN: 60376

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

African (AFR) AF: 0.676 AC: 28095 AN: 41532

American (AMR) AF: 0.916 AC: 14024 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.937 AC: 3252 AN: 3472

East Asian (EAS) AF: 0.811 AC: 4189 AN: 5166

South Asian (SAS) AF: 0.830 AC: 4008 AN: 4828

European-Finnish (FIN) AF: 0.878 AC: 9330 AN: 10626

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.914 AC: 62197 AN: 68018

Other (OTH) AF: 0.885 AC: 1870 AN: 2112

Alfa AF: 0.897 Hom.: 130786

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
PhyloP100		-1.4
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2258447; hg19: chr3-195479256; COSMIC: COSV57794598;