Variant 3-195764168-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_018406.7(MUC4):c.13925-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000368 in 1,561,516 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00037 ( 1 hom. )

Consequence

MUC4
NM_018406.7 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001424

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.01

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 3-195764168-C-T is Benign according to our data. Variant chr3-195764168-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 760451.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
MUC4	NM_018406.7 linkuse as main transcript	c.13925-4G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000463781.8
MUC4	NM_004532.6 linkuse as main transcript	c.1217-4G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
MUC4	NM_138297.5 linkuse as main transcript	c.1064-4G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC4	ENST00000463781.8 linkuse as main transcript	c.13925-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_018406.7	A2	Q99102-1

Frequencies

GnomAD3 genomes

AF:

0.000329

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000450

AC:

AN:

164344

Hom.:

AF XY:

0.000526

AC XY:

AN XY:

87514

show subpopulations

Gnomad AFR exome

AF:

0.000108

Gnomad AMR exome

AF:

0.000273

Gnomad ASJ exome

AF:

0.000117

Gnomad EAS exome

AF:

0.000165

Gnomad SAS exome

AF:

0.000469

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000770

Gnomad OTH exome

AF:

0.000437

GnomAD4 exome

AF:

0.000373

AC:

525

AN:

1409238

Hom.:

Cov.:

AF XY:

0.000383

AC XY:

267

AN XY:

696284

show subpopulations

Gnomad4 AFR exome

AF:

0.000125

Gnomad4 AMR exome

AF:

0.000244

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000548

Gnomad4 SAS exome

AF:

0.000474

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000427

Gnomad4 OTH exome

AF:

0.000154

GnomAD4 genome

AF:

0.000328

AC:

AN:

152278

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000351

Hom.:

Bravo

AF:

0.000257

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

Cadd

Benign

1.9

Dann

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000014

dbscSNV1_RF

Benign

0.0

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over