11-1226967-G-T

Variant names:

• chr11-1226967-G-T
• rs908224
• NM_002458.3:c.462-64G>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.462-64G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 1,517,360 control chromosomes in the GnomAD database, including 306,158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (28803 hom., cov: 30)
  • Exomes 𝑓: 0.63 (277355 hom.)
• Consequence: MUC5B NM_002458.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.69
• Publications: 7 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=-0.76).
• BP6: Variant 11-1226967-G-T is Benign according to our data. Variant chr11-1226967-G-T is described in ClinVar as Benign. ClinVar VariationId is 1282609.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.697 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.462-64G>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.462-64G>T		intron	N/A	ENSP00000436812.1	Q9HC84
	MUC5B	ENST00000525715.5	TSL:1	n.520-64G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.631 AC: 92643 AN: 146742 Hom.: 28771 Cov.: 30

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.590

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.635

GnomAD4 exome AF: 0.634 AC: 869176 AN: 1370510 Hom.: 277355 Cov.: 23 AF XY: 0.632 AC XY: 428298 AN XY: 677586

African (AFR) AF: 0.628 AC: 19996 AN: 31854

American (AMR) AF: 0.784 AC: 31637 AN: 40366

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 14141 AN: 24272

East Asian (EAS) AF: 0.595 AC: 22552 AN: 37924

South Asian (SAS) AF: 0.581 AC: 46453 AN: 79962

European-Finnish (FIN) AF: 0.676 AC: 32870 AN: 48620

Middle Eastern (MID) AF: 0.602 AC: 2525 AN: 4194

European-Non Finnish (NFE) AF: 0.634 AC: 663026 AN: 1046606

Other (OTH) AF: 0.634 AC: 35976 AN: 56712

GnomAD4 genome AF: 0.631 AC: 92721 AN: 146850 Hom.: 28803 Cov.: 30 AF XY: 0.635 AC XY: 45480 AN XY: 71676

African (AFR) AF: 0.622 AC: 24838 AN: 39908

American (AMR) AF: 0.709 AC: 10512 AN: 14834

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2001 AN: 3404

East Asian (EAS) AF: 0.593 AC: 2943 AN: 4966

South Asian (SAS) AF: 0.572 AC: 2690 AN: 4702

European-Finnish (FIN) AF: 0.670 AC: 6644 AN: 9918

Middle Eastern (MID) AF: 0.580 AC: 167 AN: 288

European-Non Finnish (NFE) AF: 0.622 AC: 41023 AN: 65916

Other (OTH) AF: 0.636 AC: 1306 AN: 2052

Alfa AF: 0.609 Hom.: 2945

Asia WGS AF: 0.566 AC: 1965 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.76
CADD	Benign	0.0020
DANN	Benign	0.61
PhyloP100		-1.7
Mutation Taster		=29/71	disease causing

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: rs908224; hg19: chr11-1248197; COSMIC: COSV71592710; COSMIC: COSV71592710;