rs367905040

Variant names:

• chr11-1248793-T-C
• rs367905040
• NM_002458.3:c.11913T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002458.3(MUC5B):​c.11913T>C​(p.Pro3971Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0301 in 1,532,500 control chromosomes in the GnomAD database, including 959 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (64 hom., cov: 26)
  • Exomes 𝑓: 0.030 (895 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.19
• Publications: 2 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=-0.96).
• BP6: Variant 11-1248793-T-C is Benign according to our data. Variant chr11-1248793-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 403190.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.19 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0282 (3776/133790) while in subpopulation NFE AF = 0.0358 (2218/61986). AF 95% confidence interval is 0.0345. There are 64 homozygotes in GnomAd4. There are 1879 alleles in the male GnomAd4 subpopulation. Median coverage is 26. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 64 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.11913T>C	p.Pro3971Pro	synonymous	Exon 31 of 49	NP_002449.2	Q9HC84
	MUC5B-AS1	NR_157183.1		n.56+828A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.11913T>C	p.Pro3971Pro	synonymous	Exon 31 of 49	ENSP00000436812.1	Q9HC84
	MUC5B-AS1	ENST00000532061.2	TSL:5	n.56+828A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0283 AC: 3777 AN: 133662 Hom.: 64 Cov.: 26

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.00129

Gnomad AMR AF: 0.00826

Gnomad ASJ AF: 0.0308

Gnomad EAS AF: 0.000229

Gnomad SAS AF: 0.00988

Gnomad FIN AF: 0.0796

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0358

Gnomad OTH AF: 0.0258

GnomAD2 exomes AF: 0.0250 AC: 3819 AN: 152744 AF XY: 0.0245

Gnomad AFR exome AF: 0.0133

Gnomad AMR exome AF: 0.00540

Gnomad ASJ exome AF: 0.0282

Gnomad EAS exome AF: 0.0000913

Gnomad FIN exome AF: 0.0732

Gnomad NFE exome AF: 0.0325

Gnomad OTH exome AF: 0.0229

GnomAD4 exome AF: 0.0303 AC: 42349 AN: 1398710 Hom.: 895 Cov.: 52 AF XY: 0.0296 AC XY: 20419 AN XY: 689964

African (AFR) AF: 0.0118 AC: 374 AN: 31584

American (AMR) AF: 0.00613 AC: 219 AN: 35714

Ashkenazi Jewish (ASJ) AF: 0.0291 AC: 732 AN: 25164

East Asian (EAS) AF: 0.0000560 AC: 2 AN: 35730

South Asian (SAS) AF: 0.00974 AC: 773 AN: 79380

European-Finnish (FIN) AF: 0.0726 AC: 3566 AN: 49088

Middle Eastern (MID) AF: 0.00473 AC: 26 AN: 5500

European-Non Finnish (NFE) AF: 0.0326 AC: 35129 AN: 1078628

Other (OTH) AF: 0.0264 AC: 1528 AN: 57922

GnomAD4 genome AF: 0.0282 AC: 3776 AN: 133790 Hom.: 64 Cov.: 26 AF XY: 0.0289 AC XY: 1879 AN XY: 64958

African (AFR) AF: 0.0152 AC: 528 AN: 34734

American (AMR) AF: 0.00825 AC: 112 AN: 13582

Ashkenazi Jewish (ASJ) AF: 0.0308 AC: 99 AN: 3212

East Asian (EAS) AF: 0.000230 AC: 1 AN: 4352

South Asian (SAS) AF: 0.00988 AC: 39 AN: 3946

European-Finnish (FIN) AF: 0.0796 AC: 732 AN: 9198

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 200

European-Non Finnish (NFE) AF: 0.0358 AC: 2218 AN: 61986

Other (OTH) AF: 0.0255 AC: 46 AN: 1806

Alfa AF: 0.0315 Hom.: 21

Bravo AF: 0.0207

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.6
DANN	Benign	0.46
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: rs367905040; hg19: chr11-1270023;