3-195750908-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.96

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]

ACMG classification

Verdict is Benign. Variant got -15 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_single_submitter, 1 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	UniProt
MUC4	NM_018406.7	c.15852C>T	p.Asp5284=	synonymous_variant	23/25	ENST00000463781.8
MUC4	NM_004532.6	c.3144C>T	p.Asp1048=	synonymous_variant	22/24
MUC4	NM_138297.5	c.2991C>T	p.Asp997=	synonymous_variant	21/23

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0283 AC: 4306 AN: 151998 Hom.: 197 Cov.: 28

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.: 75 AF XY: 0.00616 AC XY: 837 AN XY: 135798

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.: 33 AF XY: 0.00325 AC XY: 2364 AN XY: 727032

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.: 28 AF XY: 0.0268 AC XY: 1997 AN XY: 74388

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.: 41

Bravo AF: 0.0320

EpiCase AF: 0.000763

EpiControl AF: 0.00124

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 23, 2018

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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

Other links and lift over

dbSNP: rs79428658; hg19: chr3-195477779; COSMIC: COSV100206978;