rs2943518

Variant names:

• chr11-1247452-T-C
• rs2943518
• NM_002458.3:c.10572T>C

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.10572T>C​(p.Ser3524Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,604,788 control chromosomes in the GnomAD database, including 28,568 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2386 hom., cov: 27)
  • Exomes 𝑓: 0.17 (26182 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -4.14
• 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=-0.95).
• BP6: Variant 11-1247452-T-C is Benign according to our data. Variant chr11-1247452-T-C is described in ClinVar as Benign. ClinVar VariationId is 403164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.14 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.183 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.10572T>C	p.Ser3524Ser	synonymous	Exon 31 of 49	NP_002449.2
	MUC5B-AS1	NR_157183.1		n.56+2169A>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.10572T>C	p.Ser3524Ser	synonymous	Exon 31 of 49	ENSP00000436812.1
	MUC5B-AS1	ENST00000532061.2	TSL:5	n.56+2169A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.165 AC: 24283 AN: 147254 Hom.: 2385 Cov.: 27

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.00517

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.163

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.154

GnomAD2 exomes AF: 0.152 AC: 37502 AN: 247502 AF XY: 0.156

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.0830

Gnomad ASJ exome AF: 0.156

Gnomad EAS exome AF: 0.00345

Gnomad FIN exome AF: 0.217

Gnomad NFE exome AF: 0.183

Gnomad OTH exome AF: 0.157

GnomAD4 exome AF: 0.174 AC: 254180 AN: 1457416 Hom.: 26182 Cov.: 133 AF XY: 0.174 AC XY: 126298 AN XY: 725092

African (AFR) AF: 0.153 AC: 5096 AN: 33394

American (AMR) AF: 0.0871 AC: 3891 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 4011 AN: 26096

East Asian (EAS) AF: 0.00214 AC: 85 AN: 39692

South Asian (SAS) AF: 0.149 AC: 12810 AN: 86102

European-Finnish (FIN) AF: 0.205 AC: 10839 AN: 52852

Middle Eastern (MID) AF: 0.162 AC: 673 AN: 4144

European-Non Finnish (NFE) AF: 0.186 AC: 206552 AN: 1110372

Other (OTH) AF: 0.170 AC: 10223 AN: 60088

GnomAD4 genome AF: 0.165 AC: 24294 AN: 147372 Hom.: 2386 Cov.: 27 AF XY: 0.163 AC XY: 11724 AN XY: 71786

African (AFR) AF: 0.157 AC: 6250 AN: 39920

American (AMR) AF: 0.125 AC: 1865 AN: 14964

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 523 AN: 3404

East Asian (EAS) AF: 0.00518 AC: 26 AN: 5022

South Asian (SAS) AF: 0.139 AC: 633 AN: 4568

European-Finnish (FIN) AF: 0.216 AC: 2156 AN: 9972

Middle Eastern (MID) AF: 0.176 AC: 51 AN: 290

European-Non Finnish (NFE) AF: 0.186 AC: 12310 AN: 66286

Other (OTH) AF: 0.155 AC: 317 AN: 2042

Alfa AF: 0.174 Hom.: 1259

Bravo AF: 0.155

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	-0.95
CADD	Benign	3.7
DANN	Benign	0.84
PhyloP100		-4.1
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: rs2943518; hg19: chr11-1268682; COSMIC: COSV71594665;