rs2735727

Variant names:

• chr11-1236229-G-A
• rs2735727
• NM_002458.3:c.2881-157G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-1236229-G-A
• chr11-1236229-G-C
• chr11-1236229-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002458.3(MUC5B):​c.2881-157G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 636,530 control chromosomes in the GnomAD database, including 66,106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (14458 hom., cov: 33)
  • Exomes 𝑓: 0.45 (51648 hom.)
• Consequence: MUC5B NM_002458.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.48
• Publications: 14 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 11-1236229-G-A is Benign according to our data. Variant chr11-1236229-G-A is described in ClinVar as Benign. ClinVar VariationId is 1289456.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.2881-157G>A		intron_variant	Intron 23 of 48	ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.2881-157G>A		intron_variant	Intron 23 of 48	5	NM_002458.3	ENSP00000436812.1
MUC5B	ENST00000525715.5	n.2939-157G>A		intron_variant	Intron 23 of 25	1

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64897 AN: 151904 Hom.: 14442 Cov.: 33

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.443

GnomAD4 exome AF: 0.454 AC: 219954 AN: 484508 Hom.: 51648 AF XY: 0.452 AC XY: 112674 AN XY: 249306

African (AFR) AF: 0.306 AC: 3827 AN: 12516

American (AMR) AF: 0.552 AC: 8400 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 5661 AN: 13182

East Asian (EAS) AF: 0.710 AC: 20145 AN: 28368

South Asian (SAS) AF: 0.417 AC: 15002 AN: 35936

European-Finnish (FIN) AF: 0.494 AC: 14094 AN: 28502

Middle Eastern (MID) AF: 0.427 AC: 871 AN: 2040

European-Non Finnish (NFE) AF: 0.435 AC: 140056 AN: 322074

Other (OTH) AF: 0.446 AC: 11898 AN: 26672

GnomAD4 genome AF: 0.427 AC: 64939 AN: 152022 Hom.: 14458 Cov.: 33 AF XY: 0.435 AC XY: 32338 AN XY: 74284

African (AFR) AF: 0.314 AC: 13033 AN: 41476

American (AMR) AF: 0.538 AC: 8231 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1534 AN: 3470

East Asian (EAS) AF: 0.658 AC: 3381 AN: 5142

South Asian (SAS) AF: 0.433 AC: 2091 AN: 4830

European-Finnish (FIN) AF: 0.511 AC: 5400 AN: 10570

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29724 AN: 67936

Other (OTH) AF: 0.448 AC: 944 AN: 2106

Alfa AF: 0.430 Hom.: 14783

Bravo AF: 0.426

Asia WGS AF: 0.568 AC: 1972 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.19
DANN	Benign	0.66
PhyloP100		-3.5
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: rs2735727; hg19: chr11-1257459; COSMIC: COSV71590879;