rs201433788

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

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. 14/18 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.35

Publications

5 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 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 VariationId is 403124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC4	NM_018406.7 link	c.3718G>T	p.Ala1240Ser	missense_variant	Exon 2 of 25	ENST00000463781.8	NP_060876.5	Q99102-1E9PDY6
MUC4	NM_004532.6 link	c.83-9407G>T		intron_variant	Intron 1 of 23		NP_004523.3	Q99102-13A0T3F4
MUC4	NM_138297.5 link	c.83-13557G>T		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.3718G>T	p.Ala1240Ser	missense_variant	Exon 2 of 25	5	NM_018406.7	ENSP00000417498.3		Q99102-1E9PDY6

Frequencies

GnomAD3 genomes

AF:

0.391

AC:

890

AN:

2274

Hom.:

185

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.632

AC:

25717

AN:

40662

AF XY:

0.629

show subpopulations

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 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.:

AF XY:

0.658

AC XY:

126564

AN XY:

192406

show subpopulations

African (AFR)

AF:

0.826

AC:

6972

AN:

8440

American (AMR)

AF:

0.546

AC:

8721

AN:

15986

Ashkenazi Jewish (ASJ)

AF:

0.740

AC:

8178

AN:

11048

East Asian (EAS)

AF:

0.773

AC:

21015

AN:

27192

South Asian (SAS)

AF:

0.597

AC:

22052

AN:

36956

European-Finnish (FIN)

AF:

0.676

AC:

15530

AN:

22978

Middle Eastern (MID)

AF:

0.637

AC:

811

AN:

1274

European-Non Finnish (NFE)

AF:

0.651

AC:

145118

AN:

222988

Other (OTH)

AF:

0.687

AC:

13736

AN:

19988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.412

Heterozygous variant carriers

2734

5468

8201

10935

13669

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

980

1960

2940

3920

4900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.391

AC:

886

AN:

2268

Hom.:

183

Cov.:

AF XY:

0.387

AC XY:

416

AN XY:

1076

show subpopulations

African (AFR)

AF:

0.569

AC:

AN:

160

American (AMR)

AF:

0.349

AC:

122

AN:

350

Ashkenazi Jewish (ASJ)

AF:

0.463

AC:

AN:

East Asian (EAS)

AF:

0.396

AC:

AN:

South Asian (SAS)

AF:

0.326

AC:

AN:

European-Finnish (FIN)

AF:

0.388

AC:

AN:

170

Middle Eastern (MID)

AF:

0.375

AC:

AN:

European-Non Finnish (NFE)

AF:

0.375

AC:

479

AN:

1276

Other (OTH)

AF:

0.577

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.373

Hom.:

308

ExAC

AF:

0.190

AC:

1615

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.018

(source)

DANN

Benign

0.93

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.00020

LIST_S2

Benign

0.61

T;T

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-1.0

PhyloP100

-3.3

PrimateAI

Benign

0.46

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

gMVP

0.000014

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over