Variant rs882605 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018406.7(MUC4):c.898T>G(p.Phe300Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 1,613,774 control chromosomes in the GnomAD database, including 527,426 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.80 ( 49061 hom., cov: 31)

Exomes 𝑓: 0.81 ( 478365 hom. )

Consequence

MUC4
NM_018406.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.61

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1403313E-6).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MUC4	NM_018406.7 linkuse as main transcript	c.898T>G	p.Phe300Val	missense_variant	2/25	ENST00000463781.8
MUC4	NM_004532.6 linkuse as main transcript	c.83-12227T>G		intron_variant
MUC4	NM_138297.5 linkuse as main transcript	c.83-16377T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC4	ENST00000463781.8 linkuse as main transcript	c.898T>G	p.Phe300Val	missense_variant	2/25	5	NM_018406.7	A2	Q99102-1

Frequencies

GnomAD3 genomes

AF:

0.801

AC:

121801

AN:

151982

Hom.:

49024

Cov.:

show subpopulations

Gnomad AFR

AF:

0.816

Gnomad AMI

AF:

0.783

Gnomad AMR

AF:

0.714

Gnomad ASJ

AF:

0.845

Gnomad EAS

AF:

0.802

Gnomad SAS

AF:

0.679

Gnomad FIN

AF:

0.802

Gnomad MID

AF:

0.744

Gnomad NFE

AF:

0.818

Gnomad OTH

AF:

0.824

GnomAD3 exomes

AF:

0.776

AC:

193245

AN:

249178

Hom.:

75743

AF XY:

0.776

AC XY:

104869

AN XY:

135168

show subpopulations

Gnomad AFR exome

AF:

0.814

Gnomad AMR exome

AF:

0.633

Gnomad ASJ exome

AF:

0.841

Gnomad EAS exome

AF:

0.806

Gnomad SAS exome

AF:

0.665

Gnomad FIN exome

AF:

0.797

Gnomad NFE exome

AF:

0.828

Gnomad OTH exome

AF:

0.794

GnomAD4 exome

AF:

0.807

AC:

1179675

AN:

1461674

Hom.:

478365

Cov.:

AF XY:

0.804

AC XY:

584472

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.815

Gnomad4 AMR exome

AF:

0.638

Gnomad4 ASJ exome

AF:

0.848

Gnomad4 EAS exome

AF:

0.813

Gnomad4 SAS exome

AF:

0.669

Gnomad4 FIN exome

AF:

0.792

Gnomad4 NFE exome

AF:

0.824

Gnomad4 OTH exome

AF:

0.812

GnomAD4 genome

AF:

0.801

AC:

121886

AN:

152100

Hom.:

49061

Cov.:

AF XY:

0.797

AC XY:

59261

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.816

Gnomad4 AMR

AF:

0.713

Gnomad4 ASJ

AF:

0.845

Gnomad4 EAS

AF:

0.802

Gnomad4 SAS

AF:

0.677

Gnomad4 FIN

AF:

0.802

Gnomad4 NFE

AF:

0.818

Gnomad4 OTH

AF:

0.826

Alfa

AF:

0.825

Hom.:

105058

Bravo

AF:

0.796

TwinsUK

AF:

0.826

AC:

3064

ALSPAC

AF:

0.824

AC:

3175

ESP6500AA

AF:

0.829

AC:

3311

ESP6500EA

AF:

0.825

AC:

6880

ExAC

AF:

0.781

AC:

94339

Asia WGS

AF:

0.807

AC:

2809

AN:

3478

EpiCase

AF:

0.833

EpiControl

AF:

0.839

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.012

DANN

Benign

0.50

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.00077

LIST_S2

Benign

0.34

T;T

MetaRNN

Benign

0.0000011

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.22

PROVEAN

Benign

0.10

N;N

REVEL

Benign

0.016

Sift

Benign

1.0

T;T

Sift4G

Benign

0.68

T;T

Vest4

0.072

ClinPred

0.0037

GERP RS

-7.1

gMVP

0.025

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over