chr11-1235076-C-G

Variant names:

• chr11-1235076-C-G
• rs55771636
• NM_002458.3:c.2631-9C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002458.3(MUC5B):​c.2631-9C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0296 in 1,607,038 control chromosomes in the GnomAD database, including 892 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (61 hom., cov: 33)
  • Exomes 𝑓: 0.030 (831 hom.)
• Consequence: MUC5B NM_002458.3 intron
• Scores: Splicing: ADA: 0.0002992
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.342
• Publications: 3 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=-0.87).
• BP6: Variant 11-1235076-C-G is Benign according to our data. Variant chr11-1235076-C-G is described in ClinVar as Benign. ClinVar VariationId is 178790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0251 (3827/152286) while in subpopulation NFE AF = 0.0327 (2222/67986). AF 95% confidence interval is 0.0316. There are 61 homozygotes in GnomAd4. There are 1911 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 61 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.2631-9C>G		intron_variant	Intron 21 of 48	ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.2631-9C>G		intron_variant	Intron 21 of 48	5	NM_002458.3	ENSP00000436812.1
MUC5B	ENST00000525715.5	n.2689-9C>G		intron_variant	Intron 21 of 25	1

Frequencies

GnomAD3 genomes AF: 0.0252 AC: 3828 AN: 152168 Hom.: 61 Cov.: 33

Gnomad AFR AF: 0.0137

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00806

Gnomad FIN AF: 0.0693

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0327

Gnomad OTH AF: 0.0225

GnomAD2 exomes AF: 0.0261 AC: 6337 AN: 242402 AF XY: 0.0260

Gnomad AFR exome AF: 0.0152

Gnomad AMR exome AF: 0.00506

Gnomad ASJ exome AF: 0.0278

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0733

Gnomad NFE exome AF: 0.0339

Gnomad OTH exome AF: 0.0277

GnomAD4 exome AF: 0.0301 AC: 43768 AN: 1454752 Hom.: 831 Cov.: 32 AF XY: 0.0294 AC XY: 21286 AN XY: 723140

African (AFR) AF: 0.0121 AC: 404 AN: 33438

American (AMR) AF: 0.00571 AC: 253 AN: 44280

Ashkenazi Jewish (ASJ) AF: 0.0289 AC: 745 AN: 25780

East Asian (EAS) AF: 0.00 AC: 0 AN: 39618

South Asian (SAS) AF: 0.00954 AC: 817 AN: 85678

European-Finnish (FIN) AF: 0.0722 AC: 3722 AN: 51574

Middle Eastern (MID) AF: 0.00458 AC: 26 AN: 5676

European-Non Finnish (NFE) AF: 0.0326 AC: 36151 AN: 1108620

Other (OTH) AF: 0.0275 AC: 1650 AN: 60088

GnomAD4 genome AF: 0.0251 AC: 3827 AN: 152286 Hom.: 61 Cov.: 33 AF XY: 0.0257 AC XY: 1911 AN XY: 74468

African (AFR) AF: 0.0136 AC: 566 AN: 41556

American (AMR) AF: 0.00758 AC: 116 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00807 AC: 39 AN: 4834

European-Finnish (FIN) AF: 0.0693 AC: 736 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0327 AC: 2222 AN: 67986

Other (OTH) AF: 0.0222 AC: 47 AN: 2114

Alfa AF: 0.0293 Hom.: 23

Bravo AF: 0.0200

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

2631-9C>G in intron 21 of MUC5B: This variant is not expected to have clinical s ignificance because it has been identified in 3.2% (265/8382) of European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs55771636). -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.3
DANN	Benign	0.49
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00030
dbscSNV1_RF	Benign	0.018
SpliceAI score (max)		0.080		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: rs55771636; hg19: chr11-1256306;