rs80150964

Positions:

• chr11-1245486-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_002458.3(MUC5B):​c.8606T>C​(p.Met2869Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 (1062 hom., cov: 18)
  • Exomes 𝑓: 0.10 (32064 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC5B NM_002458.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.43

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0051601827).
• BP6: Variant 11-1245486-T-C is Benign according to our data. Variant chr11-1245486-T-C is described in ClinVar as [Benign]. Clinvar id is 403148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.8606T>C	p.Met2869Thr	missense_variant	31/49	ENST00000529681.5	NP_002449.2
MUC5B-AS1	NR_157183.1	n.57-2848A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.8606T>C	p.Met2869Thr	missense_variant	31/49	5	NM_002458.3	ENSP00000436812	P1
MUC5B-AS1	ENST00000532061.2	n.57-2848A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 8502 AN: 79860 Hom.: 1063 Cov.: 18 FAILED QC

Gnomad AFR AF: 0.0991

Gnomad AMI AF: 0.0584

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0823

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0974

Gnomad OTH AF: 0.121

GnomAD3 exomes AF: 0.207 AC: 35062 AN: 169532 Hom.: 12373 AF XY: 0.205 AC XY: 19000 AN XY: 92670

Gnomad AFR exome AF: 0.181

Gnomad AMR exome AF: 0.231

Gnomad ASJ exome AF: 0.224

Gnomad EAS exome AF: 0.526

Gnomad SAS exome AF: 0.211

Gnomad FIN exome AF: 0.111

Gnomad NFE exome AF: 0.169

Gnomad OTH exome AF: 0.220

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.104 AC: 113079 AN: 1084454 Hom.: 32064 Cov.: 41 AF XY: 0.108 AC XY: 57985 AN XY: 538972

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.152

Gnomad4 ASJ exome AF: 0.183

Gnomad4 EAS exome AF: 0.531

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.0775

Gnomad4 OTH exome AF: 0.144

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.106 AC: 8498 AN: 79882 Hom.: 1062 Cov.: 18 AF XY: 0.101 AC XY: 3871 AN XY: 38456

Gnomad4 AFR AF: 0.0994

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.0823

Gnomad4 NFE AF: 0.0974

Gnomad4 OTH AF: 0.126

Alfa AF: 0.290 Hom.: 1465

ExAC AF: 0.247 AC: 28544

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	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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	0.036
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.096
DANN	Benign	0.54
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00042	N
LIST_S2	Benign	0.12	T
MetaRNN	Benign	0.0052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.34	T
PROVEAN	Benign	1.0	N
REVEL	Benign	0.038
Sift	Benign	1.0	T
Vest4		0.0060
ClinPred		0.0013	T
GERP RS		-1.7
Varity_R		0.029
gMVP		0.75

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: rs80150964; hg19: chr11-1266716; COSMIC: COSV71589827;