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. Variant got -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

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 -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 id 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

GnomAD3 exomes AF: 0.0873 AC: 13288 AN: 152266 Hom.: 704 AF XY: 0.0868 AC XY: 7019 AN XY: 80866

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 SAS exome AF: 0.0909

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

Gnomad4 AFR exome AF: 0.0204

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.0885

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.0932

Gnomad4 FIN exome AF: 0.127

Gnomad4 NFE exome AF: 0.0708

Gnomad4 OTH exome AF: 0.0724

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

Gnomad4 AFR AF: 0.0221

Gnomad4 AMR AF: 0.0921

Gnomad4 ASJ AF: 0.0949

Gnomad4 EAS AF: 0.0573

Gnomad4 SAS AF: 0.0931

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.0744

Gnomad4 OTH AF: 0.0693

Alfa AF: 0.0689 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

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: rs2249686; hg19: chr11-1280301;