11-1247725-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_002458.3(MUC5B):​c.10845C>G​(p.Leu3615Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L3615L) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.00010 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=-7.44 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.10845C>G	p.Leu3615Leu	synonymous	Exon 31 of 49	NP_002449.2
	MUC5B-AS1	NR_157183.1		n.56+1896G>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.10845C>G	p.Leu3615Leu	synonymous	Exon 31 of 49	ENSP00000436812.1
	MUC5B-AS1	ENST00000532061.2	TSL:5	n.56+1896G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000102 AC: 15 AN: 147666 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000494

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000666

Gnomad ASJ AF: 0.000294

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000300

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000121

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000435 AC: 1 AN: 229864 AF XY: 0.00000796

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000979

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00126 AC: 1806 AN: 1435888 Hom.: 0 Cov.: 95 AF XY: 0.00120 AC XY: 859 AN XY: 714130

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

African (AFR) AF: 0.000120 AC: 4 AN: 33202

American (AMR) AF: 0.0000684 AC: 3 AN: 43838

Ashkenazi Jewish (ASJ) AF: 0.00105 AC: 27 AN: 25712

East Asian (EAS) AF: 0.00 AC: 0 AN: 39394

South Asian (SAS) AF: 0.000175 AC: 15 AN: 85584

European-Finnish (FIN) AF: 0.00171 AC: 88 AN: 51492

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4112

European-Non Finnish (NFE) AF: 0.00148 AC: 1615 AN: 1093178

Other (OTH) AF: 0.000909 AC: 54 AN: 59376

⚠️ 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: 0.000102 AC: 15 AN: 147666 Hom.: 0 Cov.: 27 AF XY: 0.0000974 AC XY: 7 AN XY: 71870

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

African (AFR) AF: 0.0000494 AC: 2 AN: 40496

American (AMR) AF: 0.0000666 AC: 1 AN: 15020

Ashkenazi Jewish (ASJ) AF: 0.000294 AC: 1 AN: 3404

East Asian (EAS) AF: 0.00 AC: 0 AN: 4908

South Asian (SAS) AF: 0.00 AC: 0 AN: 4632

European-Finnish (FIN) AF: 0.000300 AC: 3 AN: 9990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000121 AC: 8 AN: 66000

Other (OTH) AF: 0.00 AC: 0 AN: 1998

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000000492081), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 260

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.86
DANN	Benign	0.70
PhyloP100		-7.4

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;