11-1246483-C-G

Variant names:

• chr11-1246483-C-G
• rs201457576
• NM_002458.3:c.9603C>G

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.9603C>G​(p.Thr3201Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0276 in 1,608,844 control chromosomes in the GnomAD database, including 967 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (73 hom., cov: 32)
  • Exomes 𝑓: 0.028 (894 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.09
• Publications: 1 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 (REVEL=0.009).
• BP6: Variant 11-1246483-C-G is Benign according to our data. Variant chr11-1246483-C-G is described in ClinVar as Benign. ClinVar VariationId is 403155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.09 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0249 (3785/152024) while in subpopulation NFE AF = 0.0326 (2214/67932). AF 95% confidence interval is 0.0315. There are 73 homozygotes in GnomAd4. There are 1878 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 73 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.9603C>G	p.Thr3201Thr	synonymous	Exon 31 of 49	NP_002449.2
	MUC5B-AS1	NR_157183.1		n.56+3138G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.9603C>G	p.Thr3201Thr	synonymous	Exon 31 of 49	ENSP00000436812.1
	MUC5B-AS1	ENST00000532061.2	TSL:5	n.56+3138G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3786 AN: 151906 Hom.: 73 Cov.: 32

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.0292

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00791

Gnomad FIN AF: 0.0688

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0326

Gnomad OTH AF: 0.0220

GnomAD2 exomes AF: 0.0222 AC: 5489 AN: 246832 AF XY: 0.0223

Gnomad AFR exome AF: 0.0125

Gnomad AMR exome AF: 0.00430

Gnomad ASJ exome AF: 0.0240

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0652

Gnomad NFE exome AF: 0.0283

Gnomad OTH exome AF: 0.0228

GnomAD4 exome AF: 0.0278 AC: 40542 AN: 1456820 Hom.: 894 Cov.: 127 AF XY: 0.0273 AC XY: 19809 AN XY: 724856

African (AFR) AF: 0.0113 AC: 378 AN: 33320

American (AMR) AF: 0.00539 AC: 241 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.0282 AC: 736 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00913 AC: 787 AN: 86198

European-Finnish (FIN) AF: 0.0712 AC: 3791 AN: 53244

Middle Eastern (MID) AF: 0.00469 AC: 27 AN: 5762

European-Non Finnish (NFE) AF: 0.0298 AC: 33022 AN: 1107590

Other (OTH) AF: 0.0259 AC: 1560 AN: 60230

GnomAD4 genome AF: 0.0249 AC: 3785 AN: 152024 Hom.: 73 Cov.: 32 AF XY: 0.0253 AC XY: 1878 AN XY: 74284

African (AFR) AF: 0.0130 AC: 539 AN: 41466

American (AMR) AF: 0.00758 AC: 116 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0292 AC: 101 AN: 3462

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5154

South Asian (SAS) AF: 0.00792 AC: 38 AN: 4798

European-Finnish (FIN) AF: 0.0688 AC: 729 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0326 AC: 2214 AN: 67932

Other (OTH) AF: 0.0218 AC: 46 AN: 2112

Alfa AF: 0.0307 Hom.: 18

Bravo AF: 0.0199

ClinVar

ClinVar submissions as Germline

Significance: 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	-1.0
CADD	Benign	0.13
DANN	Benign	0.41
PhyloP100		-1.1
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: rs201457576; hg19: chr11-1267713; COSMIC: COSV71594264;