Variant rs2259292 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.12971G>A(p.Gly4324Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 1,580,482 control chromosomes in the GnomAD database, including 261,628 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.58 ( 25712 hom., cov: 33)

Exomes 𝑓: 0.57 ( 235916 hom. )

Consequence

MUC4
NM_018406.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.79

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=5.7244365E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC4	NM_018406.7 link	c.12971G>A	p.Gly4324Asp	missense_variant	Exon 4 of 25	ENST00000463781.8	NP_060876.5	Q99102-1E9PDY6
MUC4	NM_004532.6 link	c.263G>A	p.Gly88Asp	missense_variant	Exon 3 of 24		NP_004523.3	Q99102-13A0T3F4
MUC4	NM_138297.5 link	c.110G>A	p.Gly37Asp	missense_variant	Exon 2 of 23		NP_612154.2	Q99102-12A0T3F4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC4	ENST00000463781.8 link	c.12971G>A	p.Gly4324Asp	missense_variant	Exon 4 of 25	5	NM_018406.7	ENSP00000417498.3		Q99102-1E9PDY6

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

87836

AN:

151932

Hom.:

25686

Cov.:

show subpopulations

Gnomad AFR

AF:

0.572

Gnomad AMI

AF:

0.641

Gnomad AMR

AF:

0.539

Gnomad ASJ

AF:

0.659

Gnomad EAS

AF:

0.741

Gnomad SAS

AF:

0.525

Gnomad FIN

AF:

0.618

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.571

Gnomad OTH

AF:

0.588

GnomAD3 exomes

AF:

0.588

AC:

129333

AN:

220020

Hom.:

38427

AF XY:

0.585

AC XY:

69858

AN XY:

119344

show subpopulations

Gnomad AFR exome

AF:

0.574

Gnomad AMR exome

AF:

0.516

Gnomad ASJ exome

AF:

0.674

Gnomad EAS exome

AF:

0.747

Gnomad SAS exome

AF:

0.514

Gnomad FIN exome

AF:

0.622

Gnomad NFE exome

AF:

0.590

Gnomad OTH exome

AF:

0.591

GnomAD4 exome

AF:

0.573

AC:

817814

AN:

1428432

Hom.:

235916

Cov.:

AF XY:

0.571

AC XY:

404878

AN XY:

709074

show subpopulations

Gnomad4 AFR exome

AF:

0.575

Gnomad4 AMR exome

AF:

0.509

Gnomad4 ASJ exome

AF:

0.668

Gnomad4 EAS exome

AF:

0.729

Gnomad4 SAS exome

AF:

0.501

Gnomad4 FIN exome

AF:

0.608

Gnomad4 NFE exome

AF:

0.570

Gnomad4 OTH exome

AF:

0.582

GnomAD4 genome

AF:

0.578

AC:

87904

AN:

152050

Hom.:

25712

Cov.:

AF XY:

0.577

AC XY:

42861

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.573

Gnomad4 AMR

AF:

0.539

Gnomad4 ASJ

AF:

0.659

Gnomad4 EAS

AF:

0.741

Gnomad4 SAS

AF:

0.524

Gnomad4 FIN

AF:

0.618

Gnomad4 NFE

AF:

0.571

Gnomad4 OTH

AF:

0.592

Alfa

AF:

0.582

Hom.:

36335

Bravo

AF:

0.570

TwinsUK

AF:

0.561

AC:

2079

ALSPAC

AF:

0.563

AC:

2169

ESP6500AA

AF:

0.586

AC:

2582

ESP6500EA

AF:

0.580

AC:

4991

ExAC

AF:

0.576

AC:

69768

Asia WGS

AF:

0.681

AC:

2368

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.60

DANN

Benign

0.82

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.055

T;T;T;T

MetaRNN

Benign

0.0000057

T;T;T;T

MetaSVM

Benign

-0.93

PrimateAI

Benign

0.40

PROVEAN

Benign

0.21

N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.67

T;T;T;T

Sift4G

Benign

0.47

T;T;T;T

Polyphen

0.0060

B;B;.;.

Vest4

0.21

ClinPred

0.0063

GERP RS

-2.1

gMVP

0.24

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