Variant 11-1226641-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_002458.3(MUC5B):c.226G>T(p.Val76Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,458,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.34

Variant links:

Genes affected

MUC5B (HGNC:7516): (mucin 5B, oligomeric mucus/gel-forming) This gene encodes a member of the mucin family of proteins, which are highly glycosylated macromolecular components of mucus secretions. This family member is the major gel-forming mucin in mucus. It is a major contributor to the lubricating and viscoelastic properties of whole saliva, normal lung mucus and cervical mucus. This gene has been found to be up-regulated in some human diseases, including sinus mucosa of chronic rhinosinusitis (CRS), CRS with nasal polyposis, chronic obstructive pulmonary disease (COPD) and H. pylori-associated gastric disease, and it may be involved in the pathogenesis of these diseases. [provided by RefSeq, Jul 2010]

MUC5B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.33606428).

BS2

High AC in GnomAdExome4 at 21 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3 linkuse as main transcript	c.226G>T	p.Val76Leu	missense_variant	4/49	ENST00000529681.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5 linkuse as main transcript	c.226G>T	p.Val76Leu	missense_variant	4/49	5	NM_002458.3	P1
MUC5B	ENST00000525715.5 linkuse as main transcript	n.284G>T		non_coding_transcript_exon_variant	4/26	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000821

AC:

AN:

243674

Hom.:

AF XY:

0.00000752

AC XY:

AN XY:

132948

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000182

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1458998

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

725666

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 15, 2021

The c.226G>T (p.V76L) alteration is located in exon 4 (coding exon 4) of the MUC5B gene. This alteration results from a G to T substitution at nucleotide position 226, causing the valine (V) at amino acid position 76 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.064

Eigen

Benign

0.18

Eigen_PC

Benign

0.091

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.81

M_CAP

Benign

0.027

MetaRNN

Benign

0.34

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

0.88

N;N

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.10

Sift

Uncertain

0.014

Polyphen

0.36

Vest4

0.29

MutPred

0.33

Loss of sheet (P = 0.1501);

MVP

0.082

ClinPred

0.17

GERP RS

2.8

Varity_R

0.25

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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