11-1240410-C-T

Variant names:

• chr11-1240410-C-T
• rs2735733
• NM_002458.3:c.3970+35C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002458.3(MUC5B):​c.3970+35C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 1,540,660 control chromosomes in the GnomAD database, including 161,191 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14868 hom., cov: 33)
  • Exomes 𝑓: 0.46 (146323 hom.)
• Consequence: MUC5B NM_002458.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.57
• Publications: 25 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=-0.93).
• BP6: Variant 11-1240410-C-T is Benign according to our data. Variant chr11-1240410-C-T is described in ClinVar as Benign. ClinVar VariationId is 1251061.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.642 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.3970+35C>T		intron	N/A	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.3970+35C>T		intron	N/A	ENSP00000436812.1	Q9HC84

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65742 AN: 151860 Hom.: 14848 Cov.: 33

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.445

GnomAD2 exomes AF: 0.486 AC: 99953 AN: 205676 AF XY: 0.481

Gnomad AFR exome AF: 0.306

Gnomad AMR exome AF: 0.602

Gnomad ASJ exome AF: 0.447

Gnomad EAS exome AF: 0.663

Gnomad FIN exome AF: 0.510

Gnomad NFE exome AF: 0.456

Gnomad OTH exome AF: 0.474

GnomAD4 exome AF: 0.455 AC: 632526 AN: 1388682 Hom.: 146323 Cov.: 29 AF XY: 0.454 AC XY: 310384 AN XY: 683114

African (AFR) AF: 0.307 AC: 9721 AN: 31614

American (AMR) AF: 0.589 AC: 22640 AN: 38438

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 9564 AN: 22130

East Asian (EAS) AF: 0.697 AC: 27112 AN: 38890

South Asian (SAS) AF: 0.432 AC: 33183 AN: 76808

European-Finnish (FIN) AF: 0.504 AC: 25618 AN: 50784

Middle Eastern (MID) AF: 0.430 AC: 2346 AN: 5454

European-Non Finnish (NFE) AF: 0.447 AC: 476698 AN: 1067424

Other (OTH) AF: 0.449 AC: 25644 AN: 57140

GnomAD4 genome AF: 0.433 AC: 65790 AN: 151978 Hom.: 14868 Cov.: 33 AF XY: 0.441 AC XY: 32745 AN XY: 74276

African (AFR) AF: 0.317 AC: 13124 AN: 41436

American (AMR) AF: 0.539 AC: 8235 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1549 AN: 3468

East Asian (EAS) AF: 0.661 AC: 3406 AN: 5154

South Asian (SAS) AF: 0.439 AC: 2120 AN: 4828

European-Finnish (FIN) AF: 0.523 AC: 5531 AN: 10580

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30276 AN: 67914

Other (OTH) AF: 0.450 AC: 949 AN: 2108

Alfa AF: 0.429 Hom.: 5579

Bravo AF: 0.431

Asia WGS AF: 0.577 AC: 2004 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.23
DANN	Benign	0.33
PhyloP100		-2.6
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: rs2735733; hg19: chr11-1261640; COSMIC: COSV107533046; COSMIC: COSV107533046;