rs56344012

Variant names:

• chr11-1255237-A-G
• rs56344012
• NM_002458.3:c.15861A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-1255237-A-G
• chr11-1255237-A-C

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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 Benign/Likely_benign. ClinVar VariationId is 178794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002458.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	NM_002458.3	MANE Select	c.15861A>G	p.Pro5287Pro	synonymous	Exon 36 of 49	NP_002449.2	Q9HC84

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.15861A>G	p.Pro5287Pro	synonymous	Exon 36 of 49	ENSP00000436812.1	Q9HC84

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

GnomAD2 exomes AF: 0.0237 AC: 3335 AN: 141004 AF XY: 0.0231

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 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

African (AFR) AF: 0.0151 AC: 359 AN: 23804

American (AMR) AF: 0.00710 AC: 204 AN: 28746

Ashkenazi Jewish (ASJ) AF: 0.0424 AC: 688 AN: 16214

East Asian (EAS) AF: 0.00 AC: 0 AN: 15694

South Asian (SAS) AF: 0.00992 AC: 719 AN: 72500

European-Finnish (FIN) AF: 0.107 AC: 3396 AN: 31828

Middle Eastern (MID) AF: 0.00601 AC: 26 AN: 4328

European-Non Finnish (NFE) AF: 0.0390 AC: 33209 AN: 851466

Other (OTH) AF: 0.0361 AC: 1471 AN: 40796

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

African (AFR) AF: 0.0324 AC: 519 AN: 16008

American (AMR) AF: 0.0258 AC: 112 AN: 4340

Ashkenazi Jewish (ASJ) AF: 0.0542 AC: 99 AN: 1826

East Asian (EAS) AF: 0.000450 AC: 1 AN: 2220

South Asian (SAS) AF: 0.0218 AC: 37 AN: 1698

European-Finnish (FIN) AF: 0.200 AC: 690 AN: 3444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 110

European-Non Finnish (NFE) AF: 0.0624 AC: 2174 AN: 34866

Other (OTH) AF: 0.0548 AC: 46 AN: 840

Alfa AF: 0.0288 Hom.: 157

Bravo AF: 0.0198

Asia WGS AF: 0.00376 AC: 13 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0030
DANN	Benign	0.17
PhyloP100		-7.3
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: rs56344012; hg19: chr11-1276467;