rs61734215

Positions:

• chr11-1260702-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_002458.3(MUC5B):​c.17043C>T​(p.Cys5681=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00908 in 1,611,870 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0063 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0094 (80 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.78

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 11-1260702-C-T is Benign according to our data. Variant chr11-1260702-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 164013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1260702-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-2.78 with no splicing effect.
• BS2: High AC in GnomAd4 at 953 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.17043C>T	p.Cys5681=	synonymous_variant	48/49	ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.17043C>T	p.Cys5681=	synonymous_variant	48/49	5	NM_002458.3	ENSP00000436812	P1
MUC5B	ENST00000526859.1	c.435+860C>T		intron_variant		3		ENSP00000434539

Frequencies

GnomAD3 genomes AF: 0.00626 AC: 953 AN: 152268 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00811

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00289

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00976

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00636 AC: 1559 AN: 245154 Hom.: 9 AF XY: 0.00660 AC XY: 882 AN XY: 133648

Gnomad AFR exome AF: 0.00126

Gnomad AMR exome AF: 0.00525

Gnomad ASJ exome AF: 0.0235

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00188

Gnomad FIN exome AF: 0.00136

Gnomad NFE exome AF: 0.00903

Gnomad OTH exome AF: 0.00753

GnomAD4 exome AF: 0.00937 AC: 13675 AN: 1459484 Hom.: 80 Cov.: 32 AF XY: 0.00924 AC XY: 6708 AN XY: 725936

Gnomad4 AFR exome AF: 0.00143

Gnomad4 AMR exome AF: 0.00585

Gnomad4 ASJ exome AF: 0.0223

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00191

Gnomad4 FIN exome AF: 0.00156

Gnomad4 NFE exome AF: 0.0107

Gnomad4 OTH exome AF: 0.00986

GnomAD4 genome AF: 0.00625 AC: 953 AN: 152386 Hom.: 3 Cov.: 33 AF XY: 0.00586 AC XY: 437 AN XY: 74524

Gnomad4 AFR AF: 0.00139

Gnomad4 AMR AF: 0.00810

Gnomad4 ASJ AF: 0.0196

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00310

Gnomad4 FIN AF: 0.000753

Gnomad4 NFE AF: 0.00976

Gnomad4 OTH AF: 0.00567

Alfa AF: 0.00831 Hom.: 2

Bravo AF: 0.00703

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.0110

EpiControl AF: 0.0105

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	MUC5B: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

Cys5681Cys in exon 48 of MUC5B: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 0.9% (80/8450) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs61734215). -

MUC5B-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 31, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	4.6
DANN	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs61734215; hg19: chr11-1281932;