Variant rs2291652 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_018406.7(MUC4):c.15840C>T(p.Ile5280Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 1,613,572 control chromosomes in the GnomAD database, including 160,084 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.37 ( 12230 hom., cov: 29)

Exomes 𝑓: 0.44 ( 147854 hom. )

Consequence

MUC4
NM_018406.7 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.426

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP7

Synonymous conserved (PhyloP=0.426 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC4	NM_018406.7 link	c.15840C>T	p.Ile5280Ile	synonymous_variant	23/25	ENST00000463781.8	NP_060876.5	Q99102-1E9PDY6
MUC4	NM_004532.6 link	c.3132C>T	p.Ile1044Ile	synonymous_variant	22/24		NP_004523.3	Q99102-13A0T3F4
MUC4	NM_138297.5 link	c.2979C>T	p.Ile993Ile	synonymous_variant	21/23		NP_612154.2	Q99102-12A0T3F4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC4	ENST00000463781.8 link	c.15840C>T	p.Ile5280Ile	synonymous_variant	23/25	5	NM_018406.7	ENSP00000417498.3		Q99102-1E9PDY6

Frequencies

GnomAD3 genomes

AF:

0.367

AC:

55704

AN:

151788

Hom.:

12229

Cov.:

show subpopulations

Gnomad AFR

AF:

0.132

Gnomad AMI

AF:

0.578

Gnomad AMR

AF:

0.403

Gnomad ASJ

AF:

0.415

Gnomad EAS

AF:

0.747

Gnomad SAS

AF:

0.416

Gnomad FIN

AF:

0.479

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.447

Gnomad OTH

AF:

0.389

GnomAD3 exomes

AF:

0.444

AC:

111580

AN:

251044

Hom.:

26657

AF XY:

0.446

AC XY:

60515

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.126

Gnomad AMR exome

AF:

0.429

Gnomad ASJ exome

AF:

0.415

Gnomad EAS exome

AF:

0.750

Gnomad SAS exome

AF:

0.390

Gnomad FIN exome

AF:

0.483

Gnomad NFE exome

AF:

0.456

Gnomad OTH exome

AF:

0.440

GnomAD4 exome

AF:

0.443

AC:

647359

AN:

1461666

Hom.:

147854

Cov.:

AF XY:

0.442

AC XY:

321520

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.116

Gnomad4 AMR exome

AF:

0.424

Gnomad4 ASJ exome

AF:

0.423

Gnomad4 EAS exome

AF:

0.738

Gnomad4 SAS exome

AF:

0.389

Gnomad4 FIN exome

AF:

0.479

Gnomad4 NFE exome

AF:

0.447

Gnomad4 OTH exome

AF:

0.435

GnomAD4 genome

AF:

0.367

AC:

55722

AN:

151906

Hom.:

12230

Cov.:

AF XY:

0.370

AC XY:

27482

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.131

Gnomad4 AMR

AF:

0.403

Gnomad4 ASJ

AF:

0.415

Gnomad4 EAS

AF:

0.747

Gnomad4 SAS

AF:

0.416

Gnomad4 FIN

AF:

0.479

Gnomad4 NFE

AF:

0.447

Gnomad4 OTH

AF:

0.393

Alfa

AF:

0.431

Hom.:

24013

Bravo

AF:

0.351

Asia WGS

AF:

0.583

AC:

2025

AN:

3478

EpiCase

AF:

0.446

EpiControl

AF:

0.453

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

6.9

DANN

Benign

0.64

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