Variant chr3-195750908-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018406.7(MUC4):c.15852C>T(p.Asp5284=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00602 in 1,613,582 control chromosomes in the GnomAD database, including 394 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 198 hom., cov: 28)

Exomes 𝑓: 0.0037 ( 196 hom. )

Consequence

MUC4
NM_018406.7 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.96

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 3-195750908-G-A is Benign according to our data. Variant chr3-195750908-G-A is described in ClinVar as [Benign]. Clinvar id is 780435.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.96 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MUC4	NM_018406.7 linkuse as main transcript	c.15852C>T	p.Asp5284=	synonymous_variant	23/25	ENST00000463781.8
MUC4	NM_004532.6 linkuse as main transcript	c.3144C>T	p.Asp1048=	synonymous_variant	22/24
MUC4	NM_138297.5 linkuse as main transcript	c.2991C>T	p.Asp997=	synonymous_variant	21/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC4	ENST00000463781.8 linkuse as main transcript	c.15852C>T	p.Asp5284=	synonymous_variant	23/25	5	NM_018406.7	A2	Q99102-1

Frequencies

GnomAD3 genomes

AF:

0.0283

AC:

4306

AN:

151998

Hom.:

197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0968

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00309

Gnomad SAS

AF:

0.000624

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.000912

Gnomad OTH

AF:

0.0249

GnomAD3 exomes

AF:

0.00827

AC:

2076

AN:

250932

Hom.:

AF XY:

0.00616

AC XY:

837

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.0988

Gnomad AMR exome

AF:

0.00700

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00431

Gnomad SAS exome

AF:

0.00108

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000776

Gnomad OTH exome

AF:

0.00473

GnomAD4 exome

AF:

0.00369

AC:

5388

AN:

1461466

Hom.:

196

Cov.:

AF XY:

0.00325

AC XY:

2364

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.100

Gnomad4 AMR exome

AF:

0.00731

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00202

Gnomad4 SAS exome

AF:

0.000986

Gnomad4 FIN exome

AF:

0.000263

Gnomad4 NFE exome

AF:

0.000928

Gnomad4 OTH exome

AF:

0.00732

GnomAD4 genome

AF:

0.0284

AC:

4320

AN:

152116

Hom.:

198

Cov.:

AF XY:

0.0268

AC XY:

1997

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0968

Gnomad4 AMR

AF:

0.0107

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00310

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000912

Gnomad4 OTH

AF:

0.0247

Alfa

AF:

0.00540

Hom.:

Bravo

AF:

0.0320

EpiCase

AF:

0.000763

EpiControl

AF:

0.00124

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.24

DANN

Benign

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over