Variant 3-195764038-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_018406.7(MUC4):c.14044+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00292 in 1,607,976 control chromosomes in the GnomAD database, including 45 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 0.0041 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 41 hom. )

Consequence

MUC4
NM_018406.7 splice_region, intron

Scores

Splicing: ADA: 0.000007063

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.67

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 3-195764038-C-T is Benign according to our data. Variant chr3-195764038-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3387925.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00279 (4062/1455672) while in subpopulation MID AF= 0.055 (288/5234). AF 95% confidence interval is 0.0498. There are 41 homozygotes in gnomad4_exome. There are 2036 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
MUC4	NM_018406.7 link	c.14044+7G>A	splice_region_variant, intron_variant	ENST00000463781.8	NP_060876.5	Q99102-1E9PDY6
MUC4	NM_004532.6 link	c.1336+7G>A	splice_region_variant, intron_variant		NP_004523.3	Q99102-13A0T3F4
MUC4	NM_138297.5 link	c.1183+7G>A	splice_region_variant, intron_variant		NP_612154.2	Q99102-12A0T3F4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC4	ENST00000463781.8 link	c.14044+7G>A		splice_region_variant, intron_variant		5	NM_018406.7	ENSP00000417498.3		Q99102-1E9PDY6

Frequencies

GnomAD3 genomes

AF:

0.00415

AC:

631

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00678

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00595

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.00241

Gnomad OTH

AF:

0.00957

GnomAD3 exomes

AF:

0.00390

AC:

924

AN:

236762

Hom.:

AF XY:

0.00385

AC XY:

499

AN XY:

129628

show subpopulations

Gnomad AFR exome

AF:

0.00693

Gnomad AMR exome

AF:

0.00533

Gnomad ASJ exome

AF:

0.0200

Gnomad EAS exome

AF:

0.0000558

Gnomad SAS exome

AF:

0.00111

Gnomad FIN exome

AF:

0.000150

Gnomad NFE exome

AF:

0.00326

Gnomad OTH exome

AF:

0.0121

GnomAD4 exome

AF:

0.00279

AC:

4062

AN:

1455672

Hom.:

Cov.:

AF XY:

0.00281

AC XY:

2036

AN XY:

723466

show subpopulations

Gnomad4 AFR exome

AF:

0.00818

Gnomad4 AMR exome

AF:

0.00576

Gnomad4 ASJ exome

AF:

0.0216

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.00126

Gnomad4 FIN exome

AF:

0.0000957

Gnomad4 NFE exome

AF:

0.00196

Gnomad4 OTH exome

AF:

0.00665

GnomAD4 genome

AF:

0.00414

AC:

630

AN:

152304

Hom.:

Cov.:

AF XY:

0.00395

AC XY:

294

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00674

Gnomad4 AMR

AF:

0.00595

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00241

Gnomad4 OTH

AF:

0.00947

Alfa

AF:

0.00434

Hom.:

Bravo

AF:

0.00523

Asia WGS

AF:

0.00144

AC:

AN:

3478

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

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

MUC4: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.41

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000071

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