11-1231478-G-C

Variant names:

• chr11-1231478-G-C
• rs2735709
• NM_002458.3:c.1596G>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.1596G>C​(p.Leu532Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 1,608,528 control chromosomes in the GnomAD database, including 218,872 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (22954 hom., cov: 34)
  • Exomes 𝑓: 0.52 (195918 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.09
• Publications: 20 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=-0.9).
• BP6: Variant 11-1231478-G-C is Benign according to our data. Variant chr11-1231478-G-C is described in ClinVar as Benign. ClinVar VariationId is 163995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.643 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.1596G>C	p.Leu532Leu	synonymous	Exon 14 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.1596G>C	p.Leu532Leu	synonymous	Exon 14 of 49	ENSP00000436812.1	Q9HC84
	MUC5B	ENST00000525715.5	TSL:1	n.1654G>C		non_coding_transcript_exon	Exon 14 of 26

Frequencies

GnomAD3 genomes AF: 0.546 AC: 83072 AN: 152022 Hom.: 22922 Cov.: 34

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.552

GnomAD2 exomes AF: 0.544 AC: 131192 AN: 240944 AF XY: 0.537

Gnomad AFR exome AF: 0.574

Gnomad AMR exome AF: 0.622

Gnomad ASJ exome AF: 0.548

Gnomad EAS exome AF: 0.661

Gnomad FIN exome AF: 0.576

Gnomad NFE exome AF: 0.504

Gnomad OTH exome AF: 0.535

GnomAD4 exome AF: 0.517 AC: 752531 AN: 1456388 Hom.: 195918 Cov.: 53 AF XY: 0.515 AC XY: 373176 AN XY: 724264

African (AFR) AF: 0.577 AC: 19286 AN: 33396

American (AMR) AF: 0.619 AC: 27254 AN: 44052

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 14094 AN: 26056

East Asian (EAS) AF: 0.701 AC: 27680 AN: 39488

South Asian (SAS) AF: 0.503 AC: 43121 AN: 85706

European-Finnish (FIN) AF: 0.575 AC: 29743 AN: 51736

Middle Eastern (MID) AF: 0.529 AC: 3051 AN: 5764

European-Non Finnish (NFE) AF: 0.502 AC: 556839 AN: 1109998

Other (OTH) AF: 0.523 AC: 31463 AN: 60192

GnomAD4 genome AF: 0.547 AC: 83158 AN: 152140 Hom.: 22954 Cov.: 34 AF XY: 0.552 AC XY: 41056 AN XY: 74366

African (AFR) AF: 0.577 AC: 23969 AN: 41508

American (AMR) AF: 0.599 AC: 9153 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1901 AN: 3470

East Asian (EAS) AF: 0.662 AC: 3426 AN: 5176

South Asian (SAS) AF: 0.505 AC: 2435 AN: 4822

European-Finnish (FIN) AF: 0.588 AC: 6232 AN: 10592

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34223 AN: 67968

Other (OTH) AF: 0.555 AC: 1174 AN: 2114

Alfa AF: 0.447 Hom.: 2236

Bravo AF: 0.551

Asia WGS AF: 0.622 AC: 2161 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.17
DANN	Benign	0.40
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2735709; hg19: chr11-1252708; COSMIC: COSV71593291; COSMIC: COSV71593291;