11-1244757-C-G

Variant names:

• chr11-1244757-C-G
• rs3021158
• NM_002458.3:c.7877C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002458.3(MUC5B):​c.7877C>G​(p.Thr2626Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,601,722 control chromosomes in the GnomAD database, including 15,824 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1492 hom., cov: 30)
  • Exomes 𝑓: 0.13 (14332 hom.)
• Consequence: MUC5B NM_002458.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0390
• Publications: 15 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0075758398).
• BP6: Variant 11-1244757-C-G is Benign according to our data. Variant chr11-1244757-C-G is described in ClinVar as Benign. ClinVar VariationId is 403145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.197 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	NM_002458.3	MANE Select	c.7877C>G	p.Thr2626Arg	missense	Exon 31 of 49	NP_002449.2
	MUC5B-AS1	NR_157183.1		n.57-2119G>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.7877C>G	p.Thr2626Arg	missense	Exon 31 of 49	ENSP00000436812.1
	MUC5B-AS1	ENST00000532061.2	TSL:5	n.57-2119G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.132 AC: 19999 AN: 151244 Hom.: 1492 Cov.: 30

Gnomad AFR AF: 0.0970

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0585

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.126

GnomAD2 exomes AF: 0.156 AC: 37463 AN: 239454 AF XY: 0.152

Gnomad AFR exome AF: 0.0955

Gnomad AMR exome AF: 0.285

Gnomad ASJ exome AF: 0.136

Gnomad EAS exome AF: 0.0506

Gnomad FIN exome AF: 0.232

Gnomad NFE exome AF: 0.134

Gnomad OTH exome AF: 0.157

GnomAD4 exome AF: 0.134 AC: 193845 AN: 1450360 Hom.: 14332 Cov.: 141 AF XY: 0.134 AC XY: 96693 AN XY: 721542

African (AFR) AF: 0.0936 AC: 3126 AN: 33404

American (AMR) AF: 0.275 AC: 12261 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 3404 AN: 25884

East Asian (EAS) AF: 0.103 AC: 4098 AN: 39700

South Asian (SAS) AF: 0.145 AC: 12477 AN: 85972

European-Finnish (FIN) AF: 0.213 AC: 11058 AN: 51828

Middle Eastern (MID) AF: 0.146 AC: 834 AN: 5710

European-Non Finnish (NFE) AF: 0.126 AC: 138986 AN: 1103364

Other (OTH) AF: 0.127 AC: 7601 AN: 59868

GnomAD4 genome AF: 0.132 AC: 20007 AN: 151362 Hom.: 1492 Cov.: 30 AF XY: 0.139 AC XY: 10246 AN XY: 73940

African (AFR) AF: 0.0971 AC: 4012 AN: 41336

American (AMR) AF: 0.203 AC: 3103 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 472 AN: 3448

East Asian (EAS) AF: 0.0586 AC: 303 AN: 5168

South Asian (SAS) AF: 0.142 AC: 679 AN: 4792

European-Finnish (FIN) AF: 0.226 AC: 2370 AN: 10482

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

European-Non Finnish (NFE) AF: 0.127 AC: 8609 AN: 67574

Other (OTH) AF: 0.124 AC: 261 AN: 2100

Alfa AF: 0.0871 Hom.: 160

Bravo AF: 0.131

ESP6500AA AF: 0.0845 AC: 357

ESP6500EA AF: 0.123 AC: 1041

ExAC AF: 0.141 AC: 17070

EpiCase AF: 0.128

EpiControl AF: 0.124

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
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.58
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0076	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.039
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.063
Sift	Pathogenic	0.0	D
Vest4		0.070
ClinPred		0.0085	T
GERP RS		0.12
Varity_R		0.15
gMVP		0.35
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: rs3021158; hg19: chr11-1265987; COSMIC: COSV71590101;