rs11605113

Variant names:

• chr11-1243132-A-G
• rs11605113
• NM_002458.3:c.6252A>G

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.6252A>G​(p.Thr2084Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,606,930 control chromosomes in the GnomAD database, including 80,829 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6796 hom., cov: 27)
  • Exomes 𝑓: 0.31 (74033 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.70
• Publications: 8 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-AS1 (HGNC:53936): (MUC5B antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 11-1243132-A-G is Benign according to our data. Variant chr11-1243132-A-G is described in ClinVar as Benign. ClinVar VariationId is 403135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.7 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 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.6252A>G	p.Thr2084Thr	synonymous	Exon 31 of 49	NP_002449.2
	MUC5B-AS1	NR_157183.1		n.57-494T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.6252A>G	p.Thr2084Thr	synonymous	Exon 31 of 49	ENSP00000436812.1
	MUC5B-AS1	ENST00000532061.2	TSL:5	n.57-494T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.292 AC: 43564 AN: 149072 Hom.: 6784 Cov.: 27

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.313

GnomAD2 exomes AF: 0.327 AC: 79208 AN: 242464 AF XY: 0.325

Gnomad AFR exome AF: 0.209

Gnomad AMR exome AF: 0.310

Gnomad ASJ exome AF: 0.300

Gnomad EAS exome AF: 0.609

Gnomad FIN exome AF: 0.298

Gnomad NFE exome AF: 0.322

Gnomad OTH exome AF: 0.316

GnomAD4 exome AF: 0.313 AC: 456536 AN: 1457736 Hom.: 74033 Cov.: 116 AF XY: 0.312 AC XY: 225913 AN XY: 725118

African (AFR) AF: 0.212 AC: 7085 AN: 33420

American (AMR) AF: 0.307 AC: 13698 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 7577 AN: 26090

East Asian (EAS) AF: 0.601 AC: 23837 AN: 39684

South Asian (SAS) AF: 0.280 AC: 24168 AN: 86166

European-Finnish (FIN) AF: 0.285 AC: 15143 AN: 53114

Middle Eastern (MID) AF: 0.278 AC: 1346 AN: 4836

European-Non Finnish (NFE) AF: 0.311 AC: 344733 AN: 1109644

Other (OTH) AF: 0.315 AC: 18949 AN: 60146

GnomAD4 genome AF: 0.292 AC: 43597 AN: 149194 Hom.: 6796 Cov.: 27 AF XY: 0.293 AC XY: 21341 AN XY: 72726

African (AFR) AF: 0.217 AC: 8801 AN: 40624

American (AMR) AF: 0.331 AC: 4975 AN: 15046

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1009 AN: 3428

East Asian (EAS) AF: 0.591 AC: 2885 AN: 4882

South Asian (SAS) AF: 0.287 AC: 1348 AN: 4694

European-Finnish (FIN) AF: 0.279 AC: 2831 AN: 10164

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.308 AC: 20689 AN: 67092

Other (OTH) AF: 0.319 AC: 660 AN: 2068

Alfa AF: 0.294 Hom.: 1173

Bravo AF: 0.295

ClinVar

ClinVar submissions as Germline

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	-1.0
CADD	Benign	2.2
DANN	Benign	0.36
PhyloP100		-2.7
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: rs11605113; hg19: chr11-1264362; COSMIC: COSV71592180; COSMIC: COSV71592180;