dbSNP rs74941663: MUC4:p.Ser4120Ser (chr3-195779220-A-C) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_018406.7(MUC4):c.12360T>G(p.Ser4120Ser) 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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.203

Variant links:

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]

MUC4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
MUC4	NM_018406.7 link	c.12360T>G	p.Ser4120Ser	synonymous_variant	Exon 2 of 25	ENST00000463781.8	NP_060876.5	Q99102-1E9PDY6
MUC4	NM_004532.6 link	c.83-765T>G		intron_variant	Intron 1 of 23		NP_004523.3	Q99102-13A0T3F4
MUC4	NM_138297.5 link	c.83-4915T>G		intron_variant	Intron 1 of 22		NP_612154.2	Q99102-12A0T3F4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC4	ENST00000463781.8 link	c.12360T>G	p.Ser4120Ser	synonymous_variant	Exon 2 of 25	5	NM_018406.7	ENSP00000417498.3		Q99102-1E9PDY6

Frequencies

GnomAD3 genomes

AF:

0.447

AC:

28242

AN:

63226

Hom.:

5444

Cov.:

show subpopulations

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.:

AF XY:

0.229

AC XY:

67432

AN XY:

294936

show subpopulations

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.:

AF XY:

0.444

AC XY:

13769

AN XY:

31002

show subpopulations

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

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over