Variant 1-155192276-C-T 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_001204291.1(MUC1):c.93G>A(p.Thr31=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,613,186 control chromosomes in the GnomAD database, including 251,968 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 26289 hom., cov: 32)

Exomes 𝑓: 0.55 ( 225679 hom. )

Consequence

MUC1
NM_001204291.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0300

Variant links:

Genes affected

MUC1 (HGNC:7508): (mucin 1, cell surface associated) This gene encodes a membrane-bound protein that is a member of the mucin family. Mucins are O-glycosylated proteins that play an essential role in forming protective mucous barriers on epithelial surfaces. These proteins also play a role in intracellular signaling. This protein is expressed on the apical surface of epithelial cells that line the mucosal surfaces of many different tissues including lung, breast stomach and pancreas. This protein is proteolytically cleaved into alpha and beta subunits that form a heterodimeric complex. The N-terminal alpha subunit functions in cell-adhesion and the C-terminal beta subunit is involved in cell signaling. Overexpression, aberrant intracellular localization, and changes in glycosylation of this protein have been associated with carcinomas. This gene is known to contain a highly polymorphic variable number tandem repeats (VNTR) domain. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Feb 2011]

MUC1 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_addAF=-0.812439).

BP6

Variant 1-155192276-C-T is Benign according to our data. Variant chr1-155192276-C-T is described in ClinVar as [Benign]. Clinvar id is 1321177.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-155192276-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC1	NM_001204291.1 linkuse as main transcript	c.93G>A	p.Thr31=	synonymous_variant	2/7		NP_001191220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC1	ENST00000620103.4 linkuse as main transcript	c.66G>A	p.Thr22=	synonymous_variant	2/8	5		ENSP00000481231	A2

Frequencies

GnomAD3 genomes

AF:

0.586

AC:

88846

AN:

151722

Hom.:

26259

Cov.:

show subpopulations

Gnomad AFR

AF:

0.651

Gnomad AMI

AF:

0.422

Gnomad AMR

AF:

0.636

Gnomad ASJ

AF:

0.510

Gnomad EAS

AF:

0.781

Gnomad SAS

AF:

0.542

Gnomad FIN

AF:

0.563

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.533

Gnomad OTH

AF:

0.577

GnomAD3 exomes

AF:

0.586

AC:

147016

AN:

251084

Hom.:

44114

AF XY:

0.574

AC XY:

77917

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.654

Gnomad AMR exome

AF:

0.706

Gnomad ASJ exome

AF:

0.515

Gnomad EAS exome

AF:

0.780

Gnomad SAS exome

AF:

0.553

Gnomad FIN exome

AF:

0.562

Gnomad NFE exome

AF:

0.528

Gnomad OTH exome

AF:

0.562

GnomAD4 exome

AF:

0.552

AC:

806355

AN:

1461346

Hom.:

225679

Cov.:

AF XY:

0.549

AC XY:

398884

AN XY:

726988

show subpopulations

Gnomad4 AFR exome

AF:

0.651

Gnomad4 AMR exome

AF:

0.701

Gnomad4 ASJ exome

AF:

0.514

Gnomad4 EAS exome

AF:

0.809

Gnomad4 SAS exome

AF:

0.544

Gnomad4 FIN exome

AF:

0.561

Gnomad4 NFE exome

AF:

0.535

Gnomad4 OTH exome

AF:

0.556

GnomAD4 genome

AF:

0.586

AC:

88923

AN:

151840

Hom.:

26289

Cov.:

AF XY:

0.586

AC XY:

43445

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.652

Gnomad4 AMR

AF:

0.637

Gnomad4 ASJ

AF:

0.510

Gnomad4 EAS

AF:

0.781

Gnomad4 SAS

AF:

0.541

Gnomad4 FIN

AF:

0.563

Gnomad4 NFE

AF:

0.533

Gnomad4 OTH

AF:

0.572

Alfa

AF:

0.541

Hom.:

47722

Bravo

AF:

0.600

TwinsUK

AF:

0.521

AC:

1933

ALSPAC

AF:

0.540

AC:

2083

ESP6500AA

AF:

0.644

AC:

2839

ESP6500EA

AF:

0.535

AC:

4605

ExAC

AF:

0.578

AC:

70180

Asia WGS

AF:

0.673

AC:

2341

AN:

3478

EpiCase

AF:

0.517

EpiControl

AF:

0.513

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Tubulointerstitial kidney disease, autosomal dominant, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.3

DANN

Benign

0.53

FATHMM_MKL

Benign

0.00046

MutationTaster

Benign

1.0

P;P;P;P;P;P;P;P;P;P;P;P;P;P

GERP RS

0.30

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over