rs2075855

Variant names:

• chr11-1227730-G-A
• rs2075855
• NM_002458.3:c.723G>A

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.723G>A​(p.Thr241Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0741 in 723,098 control chromosomes in the GnomAD database, including 2,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.062 (345 hom., cov: 34)
  • Exomes 𝑓: 0.077 (1949 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.20
• Publications: 12 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=-0.75).
• BP6: Variant 11-1227730-G-A is Benign according to our data. Variant chr11-1227730-G-A is described in ClinVar as Benign. ClinVar VariationId is 178783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.2 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.085 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.723G>A	p.Thr241Thr	synonymous	Exon 7 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.723G>A	p.Thr241Thr	synonymous	Exon 7 of 49	ENSP00000436812.1	Q9HC84
	MUC5B	ENST00000525715.5	TSL:1	n.781G>A		non_coding_transcript_exon	Exon 7 of 26

Frequencies

GnomAD3 genomes AF: 0.0621 AC: 9455 AN: 152176 Hom.: 345 Cov.: 34

Gnomad AFR AF: 0.0278

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0891

Gnomad ASJ AF: 0.0919

Gnomad EAS AF: 0.0521

Gnomad SAS AF: 0.0789

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0676

Gnomad OTH AF: 0.0679

GnomAD2 exomes AF: 0.0792 AC: 12912 AN: 163074 AF XY: 0.0786

Gnomad AFR exome AF: 0.0266

Gnomad AMR exome AF: 0.123

Gnomad ASJ exome AF: 0.0836

Gnomad EAS exome AF: 0.0453

Gnomad FIN exome AF: 0.0999

Gnomad NFE exome AF: 0.0697

Gnomad OTH exome AF: 0.0765

GnomAD4 exome AF: 0.0773 AC: 44102 AN: 570804 Hom.: 1949 Cov.: 0 AF XY: 0.0774 AC XY: 23857 AN XY: 308344

African (AFR) AF: 0.0292 AC: 469 AN: 16062

American (AMR) AF: 0.121 AC: 4296 AN: 35478

Ashkenazi Jewish (ASJ) AF: 0.0845 AC: 1701 AN: 20124

East Asian (EAS) AF: 0.108 AC: 3509 AN: 32472

South Asian (SAS) AF: 0.0796 AC: 5022 AN: 63090

European-Finnish (FIN) AF: 0.101 AC: 4882 AN: 48132

Middle Eastern (MID) AF: 0.0933 AC: 381 AN: 4084

European-Non Finnish (NFE) AF: 0.0678 AC: 21720 AN: 320388

Other (OTH) AF: 0.0685 AC: 2122 AN: 30974

GnomAD4 genome AF: 0.0620 AC: 9448 AN: 152294 Hom.: 345 Cov.: 34 AF XY: 0.0649 AC XY: 4830 AN XY: 74462

African (AFR) AF: 0.0277 AC: 1151 AN: 41570

American (AMR) AF: 0.0889 AC: 1360 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0919 AC: 319 AN: 3472

East Asian (EAS) AF: 0.0522 AC: 270 AN: 5170

South Asian (SAS) AF: 0.0792 AC: 382 AN: 4826

European-Finnish (FIN) AF: 0.105 AC: 1118 AN: 10624

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0675 AC: 4593 AN: 68010

Other (OTH) AF: 0.0667 AC: 141 AN: 2114

Alfa AF: 0.0651 Hom.: 148

Bravo AF: 0.0607

Asia WGS AF: 0.0540 AC: 188 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	-0.75
CADD	Benign	0.059
DANN	Benign	0.73
PhyloP100		-3.2
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: rs2075855; hg19: chr11-1248960; COSMIC: COSV71596847; COSMIC: COSV71596847;