11-1247985-C-T

Position:

• chr11-1247985-C-T

Variant summary

Our verdict is Benign. Variant got -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. 14/19 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

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:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.11105C>T	p.Thr3702Met	missense_variant	31/49	ENST00000529681.5	NP_002449.2
MUC5B-AS1	NR_157183.1	n.56+1636G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.11105C>T	p.Thr3702Met	missense_variant	31/49	5	NM_002458.3	ENSP00000436812.1
MUC5B-AS1	ENST00000532061.2	n.56+1636G>A		intron_variant		5

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

GnomAD3 exomes AF: 0.122 AC: 30373 AN: 248622 Hom.: 3026 AF XY: 0.127 AC XY: 17195 AN XY: 134954

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 SAS exome AF: 0.155

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

Gnomad4 AFR exome AF: 0.0441

Gnomad4 AMR exome AF: 0.0652

Gnomad4 ASJ exome AF: 0.192

Gnomad4 EAS exome AF: 0.0218

Gnomad4 SAS exome AF: 0.153

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.156

Gnomad4 OTH exome AF: 0.136

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

Gnomad4 AFR AF: 0.0429

Gnomad4 AMR AF: 0.0872

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.0181

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.0890

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.104

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

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs34528873; hg19: chr11-1269215; COSMIC: COSV71593789;