rs2249686

Variant names:

• chr11-1259071-G-A
• rs2249686
• NM_002458.3:c.16713+10G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-1259071-G-A
• chr11-1259071-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002458.3(MUC5B):​c.16713+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0747 in 1,545,492 control chromosomes in the GnomAD database, including 4,771 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.067 (413 hom., cov: 32)
  • Exomes 𝑓: 0.076 (4358 hom.)
• Consequence: MUC5B NM_002458.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.279
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• interstitial lung disease

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-1259071-G-A is Benign according to our data. Variant chr11-1259071-G-A is described in ClinVar as Benign. ClinVar VariationId is 164012.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.16713+10G>A		intron_variant	Intron 44 of 48	ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.16713+10G>A		intron_variant	Intron 44 of 48	5	NM_002458.3	ENSP00000436812.1
MUC5B	ENST00000526859.1	c.348+10G>A		intron_variant	Intron 4 of 5	3		ENSP00000434539.1

Frequencies

GnomAD3 genomes AF: 0.0666 AC: 10065 AN: 151074 Hom.: 413 Cov.: 32

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.0923

Gnomad ASJ AF: 0.0949

Gnomad EAS AF: 0.0571

Gnomad SAS AF: 0.0927

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.0744

Gnomad OTH AF: 0.0705

GnomAD2 exomes AF: 0.0873 AC: 13288 AN: 152266 AF XY: 0.0868

Gnomad AFR exome AF: 0.0207

Gnomad AMR exome AF: 0.127

Gnomad ASJ exome AF: 0.0869

Gnomad EAS exome AF: 0.0488

Gnomad FIN exome AF: 0.126

Gnomad NFE exome AF: 0.0767

Gnomad OTH exome AF: 0.0862

GnomAD4 exome AF: 0.0756 AC: 105424 AN: 1394302 Hom.: 4358 Cov.: 33 AF XY: 0.0767 AC XY: 52721 AN XY: 687722

African (AFR) AF: 0.0204 AC: 645 AN: 31560

American (AMR) AF: 0.125 AC: 4449 AN: 35668

Ashkenazi Jewish (ASJ) AF: 0.0885 AC: 2223 AN: 25124

East Asian (EAS) AF: 0.106 AC: 3797 AN: 35712

South Asian (SAS) AF: 0.0932 AC: 7381 AN: 79154

European-Finnish (FIN) AF: 0.127 AC: 5821 AN: 45828

Middle Eastern (MID) AF: 0.107 AC: 583 AN: 5460

European-Non Finnish (NFE) AF: 0.0708 AC: 76335 AN: 1077922

Other (OTH) AF: 0.0724 AC: 4190 AN: 57874

GnomAD4 genome AF: 0.0665 AC: 10056 AN: 151190 Hom.: 413 Cov.: 32 AF XY: 0.0702 AC XY: 5187 AN XY: 73860

African (AFR) AF: 0.0221 AC: 908 AN: 41174

American (AMR) AF: 0.0921 AC: 1401 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.0949 AC: 328 AN: 3458

East Asian (EAS) AF: 0.0573 AC: 292 AN: 5098

South Asian (SAS) AF: 0.0931 AC: 445 AN: 4780

European-Finnish (FIN) AF: 0.132 AC: 1379 AN: 10478

Middle Eastern (MID) AF: 0.110 AC: 32 AN: 292

European-Non Finnish (NFE) AF: 0.0744 AC: 5038 AN: 67696

Other (OTH) AF: 0.0693 AC: 146 AN: 2106

Alfa AF: 0.0673 Hom.: 29

Bravo AF: 0.0621

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

16713+10G>A in intron 44 of MUC5B: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus se quence. It has been identified in 6.5% (497/7704) of European American chromosom es from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs. washington.edu/EVS; dbSNP rs2249686). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.4
DANN	Benign	0.59
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2249686; hg19: chr11-1280301;