Variant rs199812923 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_018406.7(MUC4):c.8223G>T(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. 12/17 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 0.0033 ( 0 hom., cov: 0)

Exomes 𝑓: 0.020 ( 50 hom. )

Consequence

MUC4
NM_018406.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.54

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008604169).

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0196 (6361/323824) while in subpopulation AFR AF= 0.0408 (483/11826). AF 95% confidence interval is 0.0378. There are 50 homozygotes in gnomad4_exome. There are 3189 alleles in male gnomad4_exome subpopulation. Median coverage is 8. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MUC4	NM_018406.7 linkuse as main transcript	c.8223G>T	p.Glu2741Asp	missense_variant	2/25	ENST00000463781.8	NP_060876.5
MUC4	NM_004532.6 linkuse as main transcript	c.83-4902G>T		intron_variant			NP_004523.3
MUC4	NM_138297.5 linkuse as main transcript	c.83-9052G>T		intron_variant			NP_612154.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC4	ENST00000463781.8 linkuse as main transcript	c.8223G>T	p.Glu2741Asp	missense_variant	2/25	5	NM_018406.7	ENSP00000417498	A2	Q99102-1

Frequencies

GnomAD3 genomes

AF:

0.00309

AC:

AN:

9372

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00740

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00139

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00314

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00140

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00103

AC:

AN:

45466

Hom.:

AF XY:

0.00114

AC XY:

AN XY:

23748

show subpopulations

Gnomad AFR exome

AF:

0.000454

Gnomad AMR exome

AF:

0.00134

Gnomad ASJ exome

AF:

0.000987

Gnomad EAS exome

AF:

0.000833

Gnomad SAS exome

AF:

0.000811

Gnomad FIN exome

AF:

0.000260

Gnomad NFE exome

AF:

0.00138

Gnomad OTH exome

AF:

0.00267

GnomAD4 exome

AF:

0.0196

AC:

6361

AN:

323824

Hom.:

Cov.:

AF XY:

0.0198

AC XY:

3189

AN XY:

160996

show subpopulations

Gnomad4 AFR exome

AF:

0.0408

Gnomad4 AMR exome

AF:

0.0259

Gnomad4 ASJ exome

AF:

0.0223

Gnomad4 EAS exome

AF:

0.00427

Gnomad4 SAS exome

AF:

0.0106

Gnomad4 FIN exome

AF:

0.00604

Gnomad4 NFE exome

AF:

0.0204

Gnomad4 OTH exome

AF:

0.0175

GnomAD4 genome

AF:

0.00330

AC:

AN:

9384

Hom.:

Cov.:

AF XY:

0.00428

AC XY:

AN XY:

4436

show subpopulations

Gnomad4 AFR

AF:

0.00808

Gnomad4 AMR

AF:

0.00139

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00316

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00140

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000104

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.18

DANN

Benign

0.31

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.00047

LIST_S2

Benign

0.52

T;T

M_CAP

Benign

0.00044

MetaRNN

Benign

0.0086

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N

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

MVP

0.014

ClinPred

0.0038

GERP RS

-1.4

gMVP

0.000053

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