11-1255237-A-G

Variant names:

• chr11-1255237-A-G
• rs56344012
• NM_002458.3:c.15861A>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.15861A>G​(p.Pro5287Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 1,151,180 control chromosomes in the GnomAD database, including 824 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (59 hom., cov: 18)
  • Exomes 𝑓: 0.037 (765 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -7.33

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP6: Variant 11-1255237-A-G is Benign according to our data. Variant chr11-1255237-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 178794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1255237-A-G is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-7.32 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.15861A>G	p.Pro5287Pro	synonymous_variant	Exon 36 of 49	ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.15861A>G	p.Pro5287Pro	synonymous_variant	Exon 36 of 49	5	NM_002458.3	ENSP00000436812.1

Frequencies

GnomAD3 genomes AF: 0.0560 AC: 3680 AN: 65764 Hom.: 59 Cov.: 18

Gnomad AFR AF: 0.0326

Gnomad AMI AF: 0.00221

Gnomad AMR AF: 0.0259

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.000449

Gnomad SAS AF: 0.0218

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0623

Gnomad OTH AF: 0.0550

GnomAD3 exomes AF: 0.0237 AC: 3335 AN: 141004 Hom.: 72 AF XY: 0.0231 AC XY: 1728 AN XY: 74872

Gnomad AFR exome AF: 0.0142

Gnomad AMR exome AF: 0.00519

Gnomad ASJ exome AF: 0.0274

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00916

Gnomad FIN exome AF: 0.0712

Gnomad NFE exome AF: 0.0297

Gnomad OTH exome AF: 0.0228

GnomAD4 exome AF: 0.0369 AC: 40072 AN: 1085376 Hom.: 765 Cov.: 36 AF XY: 0.0361 AC XY: 19280 AN XY: 534404

Gnomad4 AFR exome AF: 0.0151

Gnomad4 AMR exome AF: 0.00710

Gnomad4 ASJ exome AF: 0.0424

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00992

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.0390

Gnomad4 OTH exome AF: 0.0361

GnomAD4 genome AF: 0.0559 AC: 3679 AN: 65804 Hom.: 59 Cov.: 18 AF XY: 0.0582 AC XY: 1819 AN XY: 31268

Gnomad4 AFR AF: 0.0324

Gnomad4 AMR AF: 0.0258

Gnomad4 ASJ AF: 0.0542

Gnomad4 EAS AF: 0.000450

Gnomad4 SAS AF: 0.0218

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.0624

Gnomad4 OTH AF: 0.0548

Alfa AF: 0.0299 Hom.: 47

Bravo AF: 0.0198

Asia WGS AF: 0.00376 AC: 13 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Jun 03, 2014

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Pro5287Pro in exon 36 of MUC5B: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 7.0% (13/186) of F innish chromosomes from a broad population by the 1000 Genomes Project (http://w ww.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs56344012). -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely 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	-1.0
CADD	Benign	0.0030
DANN	Benign	0.17

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: rs56344012; hg19: chr11-1276467;