rs2943523

Variant names:

• chr11-1247725-C-T
• rs2943523
• NM_002458.3:c.10845C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-1247725-C-T
• chr11-1247725-C-A
• chr11-1247725-C-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.10845C>T​(p.Leu3615Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,588,130 control chromosomes in the GnomAD database, including 23,127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1831 hom., cov: 27)
  • Exomes 𝑓: 0.14 (21296 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -7.44
• 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-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=-0.87).
• BP6: Variant 11-1247725-C-T is Benign according to our data. Variant chr11-1247725-C-T is described in ClinVar as Benign. ClinVar VariationId is 403166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-7.44 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.2 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.10845C>T	p.Leu3615Leu	synonymous	Exon 31 of 49	NP_002449.2	Q9HC84
	MUC5B-AS1	NR_157183.1		n.56+1896G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.10845C>T	p.Leu3615Leu	synonymous	Exon 31 of 49	ENSP00000436812.1	Q9HC84
	MUC5B-AS1	ENST00000532061.2	TSL:5	n.56+1896G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.133 AC: 19679 AN: 147658 Hom.: 1831 Cov.: 27

Gnomad AFR AF: 0.0873

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0609

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.129

GnomAD2 exomes AF: 0.162 AC: 37149 AN: 229864 AF XY: 0.156

Gnomad AFR exome AF: 0.0894

Gnomad AMR exome AF: 0.292

Gnomad ASJ exome AF: 0.138

Gnomad EAS exome AF: 0.0552

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.139

Gnomad OTH exome AF: 0.159

GnomAD4 exome AF: 0.137 AC: 198015 AN: 1440354 Hom.: 21296 Cov.: 95 AF XY: 0.138 AC XY: 98764 AN XY: 716232

African (AFR) AF: 0.0834 AC: 2770 AN: 33230

American (AMR) AF: 0.282 AC: 12349 AN: 43808

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 3453 AN: 25762

East Asian (EAS) AF: 0.104 AC: 4114 AN: 39390

South Asian (SAS) AF: 0.146 AC: 12483 AN: 85620

European-Finnish (FIN) AF: 0.227 AC: 11733 AN: 51592

Middle Eastern (MID) AF: 0.148 AC: 609 AN: 4108

European-Non Finnish (NFE) AF: 0.130 AC: 142814 AN: 1097344

Other (OTH) AF: 0.129 AC: 7690 AN: 59500

GnomAD4 genome AF: 0.133 AC: 19674 AN: 147776 Hom.: 1831 Cov.: 27 AF XY: 0.140 AC XY: 10102 AN XY: 71996

African (AFR) AF: 0.0870 AC: 3534 AN: 40598

American (AMR) AF: 0.206 AC: 3097 AN: 15032

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 479 AN: 3406

East Asian (EAS) AF: 0.0611 AC: 299 AN: 4894

South Asian (SAS) AF: 0.145 AC: 669 AN: 4628

European-Finnish (FIN) AF: 0.244 AC: 2435 AN: 9992

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8707 AN: 66010

Other (OTH) AF: 0.127 AC: 257 AN: 2020

Alfa AF: 0.0930 Hom.: 260

Bravo AF: 0.129

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	-0.87
CADD	Benign	2.9
DANN	Benign	0.82
PhyloP100		-7.4
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: rs2943523; hg19: chr11-1268955; COSMIC: COSV71590103;