rs12286473

chr11-1243660-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002458.3(MUC5B):c.6780A>G(p.Arg2260=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,576,616 control chromosomes in the GnomAD database, including 24,270 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1442 hom., cov: 29)
  • Exomes 𝑓: 0.16 (22828 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.54

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-AS1 (HGNC:53936): (MUC5B antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.09).
• BP6: Variant 11-1243660-A-G is Benign according to our data. Variant chr11-1243660-A-G is described in ClinVar as [Benign]. Clinvar id is 403141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.54 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3	c.6780A>G	p.Arg2260=	synonymous_variant	31/49	ENST00000529681.5
MUC5B-AS1	NR_157183.1	n.57-1022T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5	c.6780A>G	p.Arg2260=	synonymous_variant	31/49	5	NM_002458.3	P1
MUC5B-AS1	ENST00000532061.2	n.57-1022T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18649 AN: 149074 Hom.: 1441 Cov.: 29

Gnomad AFR AF: 0.0533

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.0949

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.0180

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.128

GnomAD3 exomes AF: 0.129 AC: 30996 AN: 240444 Hom.: 3070 AF XY: 0.134 AC XY: 17445 AN XY: 130284

Gnomad AFR exome AF: 0.0489

Gnomad AMR exome AF: 0.0622

Gnomad ASJ exome AF: 0.192

Gnomad EAS exome AF: 0.0159

Gnomad SAS exome AF: 0.156

Gnomad FIN exome AF: 0.129

Gnomad NFE exome AF: 0.166

Gnomad OTH exome AF: 0.141

GnomAD4 exome AF: 0.164 AC: 234461 AN: 1427426 Hom.: 22828 Cov.: 170 AF XY: 0.165 AC XY: 117322 AN XY: 710972

Gnomad4 AFR exome AF: 0.0538

Gnomad4 AMR exome AF: 0.0707

Gnomad4 ASJ exome AF: 0.215

Gnomad4 EAS exome AF: 0.0219

Gnomad4 SAS exome AF: 0.161

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.176

Gnomad4 OTH exome AF: 0.156

GnomAD4 genome AF: 0.125 AC: 18637 AN: 149190 Hom.: 1442 Cov.: 29 AF XY: 0.121 AC XY: 8836 AN XY: 72786

Gnomad4 AFR AF: 0.0530

Gnomad4 AMR AF: 0.0947

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.0181

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.125

Alfa AF: 0.164 Hom.: 979

Bravo AF: 0.122

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	1.9
Dann	Benign	0.15

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

Other links and lift over

dbSNP: rs12286473; hg19: chr11-1264890; COSMIC: COSV71590439; COSMIC: COSV71590439;