rs74941663

Positions:

• chr3-195779220-A-C
• chr3-195779220-A-G
• chr3-195779220-A-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_018406.7(MUC4):​c.12360T>G​(p.Ser4120=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (5448 hom., cov: 10)
  • Exomes 𝑓: 0.24 (31935 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC4 NM_018406.7 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.203

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.16).
• BP6: Variant 3-195779220-A-C is Benign according to our data. Variant chr3-195779220-A-C is described in ClinVar as [Benign]. Clinvar id is 403118.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.203 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC4	NM_018406.7	c.12360T>G	p.Ser4120=	synonymous_variant	2/25	ENST00000463781.8
MUC4	NM_004532.6	c.83-765T>G		intron_variant
MUC4	NM_138297.5	c.83-4915T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC4	ENST00000463781.8	c.12360T>G	p.Ser4120=	synonymous_variant	2/25	5	NM_018406.7	A2

Frequencies

GnomAD3 genomes AF: 0.447 AC: 28242 AN: 63226 Hom.: 5444 Cov.: 10

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.455

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.236 AC: 140416 AN: 596116 Hom.: 31935 Cov.: 52 AF XY: 0.229 AC XY: 67432 AN XY: 294936

Gnomad4 AFR exome AF: 0.220

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.302

Gnomad4 EAS exome AF: 0.217

Gnomad4 SAS exome AF: 0.134

Gnomad4 FIN exome AF: 0.232

Gnomad4 NFE exome AF: 0.248

Gnomad4 OTH exome AF: 0.236

GnomAD4 genome AF: 0.447 AC: 28261 AN: 63292 Hom.: 5448 Cov.: 10 AF XY: 0.444 AC XY: 13769 AN XY: 31002

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.623

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.460

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.2
CADD	Benign	1.5
DANN	Benign	0.20

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: rs74941663; hg19: chr3-195506091; COSMIC: COSV57778184; COSMIC: COSV57778184;