chr11-1260702-C-T

Variant names:

• chr11-1260702-C-T
• rs61734215
• NM_002458.3:c.17043C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_002458.3(MUC5B):​c.17043C>T​(p.Cys5681Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00908 in 1,611,870 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0063 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0094 (80 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.78
• Publications: 5 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 11-1260702-C-T is Benign according to our data. Variant chr11-1260702-C-T is described in ClinVar as Benign. ClinVar VariationId is 164013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.78 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.17043C>T	p.Cys5681Cys	synonymous	Exon 48 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.17043C>T	p.Cys5681Cys	synonymous	Exon 48 of 49	ENSP00000436812.1	Q9HC84
	MUC5B	ENST00000526859.1	TSL:3	c.435+860C>T		intron	N/A	ENSP00000434539.1	H0YDX8

Frequencies

GnomAD3 genomes AF: 0.00626 AC: 953 AN: 152268 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00811

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00289

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00976

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00636 AC: 1559 AN: 245154 AF XY: 0.00660

Gnomad AFR exome AF: 0.00126

Gnomad AMR exome AF: 0.00525

Gnomad ASJ exome AF: 0.0235

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00136

Gnomad NFE exome AF: 0.00903

Gnomad OTH exome AF: 0.00753

GnomAD4 exome AF: 0.00937 AC: 13675 AN: 1459484 Hom.: 80 Cov.: 32 AF XY: 0.00924 AC XY: 6708 AN XY: 725936

African (AFR) AF: 0.00143 AC: 48 AN: 33464

American (AMR) AF: 0.00585 AC: 261 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.0223 AC: 583 AN: 26112

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39662

South Asian (SAS) AF: 0.00191 AC: 164 AN: 86034

European-Finnish (FIN) AF: 0.00156 AC: 81 AN: 52044

Middle Eastern (MID) AF: 0.0109 AC: 63 AN: 5764

European-Non Finnish (NFE) AF: 0.0107 AC: 11878 AN: 1111468

Other (OTH) AF: 0.00986 AC: 595 AN: 60318

GnomAD4 genome AF: 0.00625 AC: 953 AN: 152386 Hom.: 3 Cov.: 33 AF XY: 0.00586 AC XY: 437 AN XY: 74524

African (AFR) AF: 0.00139 AC: 58 AN: 41600

American (AMR) AF: 0.00810 AC: 124 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00310 AC: 15 AN: 4832

European-Finnish (FIN) AF: 0.000753 AC: 8 AN: 10626

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00976 AC: 664 AN: 68038

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.00902 Hom.: 7

Bravo AF: 0.00703

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.0110

EpiControl AF: 0.0105

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	MUC5B-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	4.6
DANN	Benign	0.92
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs61734215; hg19: chr11-1281932;