rs34528873

Variant names:

• chr11-1247985-C-T
• rs34528873
• NM_002458.3:c.11105C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-1247985-C-T
• chr11-1247985-C-A
• chr11-1247985-C-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.11105C>T​(p.Thr3702Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,610,244 control chromosomes in the GnomAD database, including 22,542 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1312 hom., cov: 26)
  • Exomes 𝑓: 0.14 (21230 hom.)
• Consequence: MUC5B NM_002458.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.49
• Publications: 13 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=0.001190722).
• BP6: Variant 11-1247985-C-T is Benign according to our data. Variant chr11-1247985-C-T is described in ClinVar as Benign. ClinVar VariationId is 403167.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.148 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.11105C>T	p.Thr3702Met	missense	Exon 31 of 49	NP_002449.2	Q9HC84
	MUC5B-AS1	NR_157183.1		n.56+1636G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.11105C>T	p.Thr3702Met	missense	Exon 31 of 49	ENSP00000436812.1	Q9HC84
	MUC5B-AS1	ENST00000532061.2	TSL:5	n.56+1636G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.106 AC: 15988 AN: 150894 Hom.: 1311 Cov.: 26

Gnomad AFR AF: 0.0431

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.0874

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.0180

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0890

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.107

GnomAD2 exomes AF: 0.122 AC: 30373 AN: 248622 AF XY: 0.127

Gnomad AFR exome AF: 0.0436

Gnomad AMR exome AF: 0.0635

Gnomad ASJ exome AF: 0.186

Gnomad EAS exome AF: 0.0160

Gnomad FIN exome AF: 0.102

Gnomad NFE exome AF: 0.157

Gnomad OTH exome AF: 0.133

GnomAD4 exome AF: 0.144 AC: 210614 AN: 1459232 Hom.: 21230 Cov.: 90 AF XY: 0.145 AC XY: 105432 AN XY: 725956

African (AFR) AF: 0.0441 AC: 1477 AN: 33462

American (AMR) AF: 0.0652 AC: 2915 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 5017 AN: 26114

East Asian (EAS) AF: 0.0218 AC: 864 AN: 39698

South Asian (SAS) AF: 0.153 AC: 13176 AN: 86230

European-Finnish (FIN) AF: 0.103 AC: 5454 AN: 52786

Middle Eastern (MID) AF: 0.150 AC: 858 AN: 5720

European-Non Finnish (NFE) AF: 0.156 AC: 172672 AN: 1110232

Other (OTH) AF: 0.136 AC: 8181 AN: 60286

GnomAD4 genome AF: 0.106 AC: 15978 AN: 151012 Hom.: 1312 Cov.: 26 AF XY: 0.103 AC XY: 7572 AN XY: 73736

African (AFR) AF: 0.0429 AC: 1769 AN: 41224

American (AMR) AF: 0.0872 AC: 1327 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 613 AN: 3448

East Asian (EAS) AF: 0.0181 AC: 93 AN: 5152

South Asian (SAS) AF: 0.147 AC: 701 AN: 4782

European-Finnish (FIN) AF: 0.0890 AC: 927 AN: 10416

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10153 AN: 67468

Other (OTH) AF: 0.104 AC: 219 AN: 2100

Alfa AF: 0.111 Hom.: 298

Bravo AF: 0.103

ESP6500AA AF: 0.0426 AC: 174

ESP6500EA AF: 0.158 AC: 1311

ExAC AF: 0.125 AC: 15076

ClinVar

ClinVar submissions

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	0.10
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.0
DANN	Benign	0.66
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.0012	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		-2.5
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.064
Sift	Uncertain	0.0010	D
Vest4		0.026
ClinPred		0.0053	T
GERP RS		-0.73
Varity_R		0.025
gMVP		0.41
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: rs34528873; hg19: chr11-1269215; COSMIC: COSV71593789;