NM_002458.3:c.6600A>G

Variant names:

• chr11-1243480-A-G
• rs59373058
• NM_002458.3:c.6600A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_002458.3(MUC5B):​c.6600A>G​(p.Arg2200Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.057 (224 hom., cov: 19)
  • Exomes 𝑓: 0.17 (73565 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.20
• Publications: 6 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 11-1243480-A-G is Benign according to our data. Variant chr11-1243480-A-G is described in ClinVar as Benign. ClinVar VariationId is 403138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.2 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	NM_002458.3	MANE Select	c.6600A>G	p.Arg2200Arg	synonymous	Exon 31 of 49	NP_002449.2
	MUC5B-AS1	NR_157183.1		n.57-842T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.6600A>G	p.Arg2200Arg	synonymous	Exon 31 of 49	ENSP00000436812.1
	MUC5B-AS1	ENST00000532061.2	TSL:5	n.57-842T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0566 AC: 5352 AN: 94504 Hom.: 221 Cov.: 19

Gnomad AFR AF: 0.0411

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0727

Gnomad ASJ AF: 0.0592

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.0465

Gnomad FIN AF: 0.0709

Gnomad MID AF: 0.0773

Gnomad NFE AF: 0.0592

Gnomad OTH AF: 0.0568

GnomAD2 exomes AF: 0.110 AC: 20414 AN: 185632 AF XY: 0.109

Gnomad AFR exome AF: 0.0648

Gnomad AMR exome AF: 0.108

Gnomad ASJ exome AF: 0.0864

Gnomad EAS exome AF: 0.390

Gnomad FIN exome AF: 0.0597

Gnomad NFE exome AF: 0.0976

Gnomad OTH exome AF: 0.109

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.173 AC: 173019 AN: 999374 Hom.: 73565 Cov.: 104 AF XY: 0.171 AC XY: 84989 AN XY: 497640

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0963 AC: 2393 AN: 24840

American (AMR) AF: 0.187 AC: 5678 AN: 30366

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 2777 AN: 17640

East Asian (EAS) AF: 0.621 AC: 14007 AN: 22544

South Asian (SAS) AF: 0.140 AC: 8387 AN: 59894

European-Finnish (FIN) AF: 0.155 AC: 5713 AN: 36854

Middle Eastern (MID) AF: 0.119 AC: 358 AN: 3006

European-Non Finnish (NFE) AF: 0.166 AC: 126441 AN: 763996

Other (OTH) AF: 0.181 AC: 7265 AN: 40234

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0568 AC: 5372 AN: 94604 Hom.: 224 Cov.: 19 AF XY: 0.0589 AC XY: 2707 AN XY: 45944

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0413 AC: 1202 AN: 29116

American (AMR) AF: 0.0728 AC: 674 AN: 9254

Ashkenazi Jewish (ASJ) AF: 0.0592 AC: 128 AN: 2162

East Asian (EAS) AF: 0.131 AC: 226 AN: 1726

South Asian (SAS) AF: 0.0468 AC: 138 AN: 2948

European-Finnish (FIN) AF: 0.0709 AC: 439 AN: 6196

Middle Eastern (MID) AF: 0.0769 AC: 16 AN: 208

European-Non Finnish (NFE) AF: 0.0592 AC: 2440 AN: 41200

Other (OTH) AF: 0.0642 AC: 81 AN: 1262

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.180 Hom.: 1107

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	-0.93
CADD	Benign	2.6
DANN	Benign	0.59
PhyloP100		-2.2
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: rs59373058; hg19: chr11-1264710; COSMIC: COSV71590137; COSMIC: COSV71590137;