3-195783357-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018406.7(MUC4):c.8223G>C(p.Glu2741Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 1009 hom., cov: 0)

Exomes 𝑓: 0.28 ( 17649 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: -3.54

Publications

10 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.061409E-5).

BP6

Variant 3-195783357-C-G is Benign according to our data. Variant chr3-195783357-C-G is described in ClinVar as Benign. ClinVar VariationId is 403121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC4	NM_018406.7 link	c.8223G>C	p.Glu2741Asp	missense_variant	Exon 2 of 25	ENST00000463781.8	NP_060876.5	Q99102-1E9PDY6
MUC4	NM_004532.6 link	c.83-4902G>C		intron_variant	Intron 1 of 23		NP_004523.3	Q99102-13A0T3F4
MUC4	NM_138297.5 link	c.83-9052G>C		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.8223G>C	p.Glu2741Asp	missense_variant	Exon 2 of 25	5	NM_018406.7	ENSP00000417498.3		Q99102-1E9PDY6

Frequencies

GnomAD3 genomes

AF:

0.493

AC:

4482

AN:

9094

Hom.:

1011

Cov.:

show subpopulations

Gnomad AFR

AF:

0.636

Gnomad AMI

AF:

0.345

Gnomad AMR

AF:

0.409

Gnomad ASJ

AF:

0.482

Gnomad EAS

AF:

0.423

Gnomad SAS

AF:

0.455

Gnomad FIN

AF:

0.443

Gnomad MID

AF:

0.625

Gnomad NFE

AF:

0.428

Gnomad OTH

AF:

0.462

GnomAD2 exomes

AF:

0.579

AC:

26311

AN:

45466

AF XY:

0.594

show subpopulations

Gnomad AFR exome

AF:

0.650

Gnomad AMR exome

AF:

0.592

Gnomad ASJ exome

AF:

0.646

Gnomad EAS exome

AF:

0.537

Gnomad FIN exome

AF:

0.486

Gnomad NFE exome

AF:

0.575

Gnomad OTH exome

AF:

0.590

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.282

AC:

87039

AN:

308552

Hom.:

17649

Cov.:

AF XY:

0.298

AC XY:

45683

AN XY:

153286

show subpopulations

African (AFR)

AF:

0.570

AC:

6848

AN:

12010

American (AMR)

AF:

0.469

AC:

3559

AN:

7594

Ashkenazi Jewish (ASJ)

AF:

0.389

AC:

2154

AN:

5534

East Asian (EAS)

AF:

0.339

AC:

3027

AN:

8926

South Asian (SAS)

AF:

0.449

AC:

9019

AN:

20090

European-Finnish (FIN)

AF:

0.538

AC:

5206

AN:

9672

Middle Eastern (MID)

AF:

0.415

AC:

339

AN:

816

European-Non Finnish (NFE)

AF:

0.227

AC:

52424

AN:

230662

Other (OTH)

AF:

0.337

AC:

4463

AN:

13248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.576

Heterozygous variant carriers

1034

2068

3101

4135

5169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1028

2056

3084

4112

5140

<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

AF:

0.492

AC:

4483

AN:

9106

Hom.:

1009

Cov.:

AF XY:

0.481

AC XY:

2064

AN XY:

4292

show subpopulations

African (AFR)

AF:

0.635

AC:

1746

AN:

2750

American (AMR)

AF:

0.408

AC:

287

AN:

704

Ashkenazi Jewish (ASJ)

AF:

0.482

AC:

159

AN:

330

East Asian (EAS)

AF:

0.419

AC:

129

AN:

308

South Asian (SAS)

AF:

0.448

AC:

AN:

134

European-Finnish (FIN)

AF:

0.443

AC:

227

AN:

512

Middle Eastern (MID)

AF:

0.625

AC:

AN:

European-Non Finnish (NFE)

AF:

0.429

AC:

1785

AN:

4164

Other (OTH)

AF:

0.462

AC:

AN:

130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.595

Heterozygous variant carriers

178

268

357

446

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.00

Hom.:

ExAC

AF:

0.522

AC:

10034

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: Does not pass quality filter, gene not related to pt phenotype -

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

0.059

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.19

(source)

DANN

Benign

0.28

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.00034

LIST_S2

Benign

0.52

T;T

MetaRNN

Benign

0.000091

T;T

MetaSVM

Benign

-1.0

PhyloP100

-3.5

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.27

N;N

REVEL

Benign

0.0060

Sift

Benign

1.0

T;T

Sift4G

Benign

0.54

T;T

Vest4

0.047

ClinPred

0.0035

GERP RS

-1.4

gMVP

0.000053

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

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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