rs201433788

Positions:

• chr3-195787862-C-A
• chr3-195787862-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_018406.7(MUC4):​c.3718G>T​(p.Ala1240Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (183 hom., cov: 0)
  • Exomes 𝑓: 0.66 (81018 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC4 NM_018406.7 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.35

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016600192).
• BP6: Variant 3-195787862-C-A is Benign according to our data. Variant chr3-195787862-C-A is described in ClinVar as [Benign]. Clinvar id is 403124.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC4	NM_018406.7	c.3718G>T	p.Ala1240Ser	missense_variant	2/25	ENST00000463781.8
MUC4	NM_004532.6	c.83-9407G>T		intron_variant
MUC4	NM_138297.5	c.83-13557G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC4	ENST00000463781.8	c.3718G>T	p.Ala1240Ser	missense_variant	2/25	5	NM_018406.7	A2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 890 AN: 2274 Hom.: 185 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.577

GnomAD3 exomes AF: 0.632 AC: 25717 AN: 40662 Hom.: 8738 AF XY: 0.629 AC XY: 13021 AN XY: 20704

Gnomad AFR exome AF: 0.810

Gnomad AMR exome AF: 0.520

Gnomad ASJ exome AF: 0.721

Gnomad EAS exome AF: 0.770

Gnomad SAS exome AF: 0.535

Gnomad FIN exome AF: 0.557

Gnomad NFE exome AF: 0.621

Gnomad OTH exome AF: 0.643

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.660 AC: 242133 AN: 366850 Hom.: 81018 Cov.: 4 AF XY: 0.658 AC XY: 126564 AN XY: 192406

Gnomad4 AFR exome AF: 0.826

Gnomad4 AMR exome AF: 0.546

Gnomad4 ASJ exome AF: 0.740

Gnomad4 EAS exome AF: 0.773

Gnomad4 SAS exome AF: 0.597

Gnomad4 FIN exome AF: 0.676

Gnomad4 NFE exome AF: 0.651

Gnomad4 OTH exome AF: 0.687

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.391 AC: 886 AN: 2268 Hom.: 183 Cov.: 0 AF XY: 0.387 AC XY: 416 AN XY: 1076

Gnomad4 AFR AF: 0.569

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.396

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.577

Alfa AF: 0.373 Hom.: 308

ExAC AF: 0.190 AC: 1615

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_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.018
DANN	Benign	0.93
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.00020	N
LIST_S2	Benign	0.61	T;T
MetaRNN	Benign	0.0017	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.10	N;N
REVEL	Benign	0.11
Sift	Benign	0.72	T;T
Sift4G	Benign	0.87	T;T
Vest4		0.093
ClinPred		0.0028	T
gMVP		0.000014

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: rs201433788; hg19: chr3-195514733; COSMIC: COSV62127965;