rs60268710

Positions:

• chr11-1246332-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.9452C>T​(p.Thr3151Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,612,516 control chromosomes in the GnomAD database, including 81,152 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6846 hom., cov: 31)
  • Exomes 𝑓: 0.31 (74306 hom.)
• Consequence: MUC5B NM_002458.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.10

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.736798E-5).
• BP6: Variant 11-1246332-C-T is Benign according to our data. Variant chr11-1246332-C-T is described in ClinVar as [Benign]. Clinvar id is 403151.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.9452C>T	p.Thr3151Met	missense_variant	31/49	ENST00000529681.5	NP_002449.2
MUC5B-AS1	NR_157183.1	n.56+3289G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.9452C>T	p.Thr3151Met	missense_variant	31/49	5	NM_002458.3	ENSP00000436812	P1
MUC5B-AS1	ENST00000532061.2	n.56+3289G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44102 AN: 151132 Hom.: 6832 Cov.: 31

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.313

GnomAD3 exomes AF: 0.322 AC: 80076 AN: 248712 Hom.: 13939 AF XY: 0.320 AC XY: 43233 AN XY: 134998

Gnomad AFR exome AF: 0.207

Gnomad AMR exome AF: 0.308

Gnomad ASJ exome AF: 0.298

Gnomad EAS exome AF: 0.609

Gnomad SAS exome AF: 0.284

Gnomad FIN exome AF: 0.287

Gnomad NFE exome AF: 0.316

Gnomad OTH exome AF: 0.313

GnomAD4 exome AF: 0.313 AC: 457578 AN: 1461266 Hom.: 74306 Cov.: 122 AF XY: 0.312 AC XY: 226464 AN XY: 726920

Gnomad4 AFR exome AF: 0.210

Gnomad4 AMR exome AF: 0.307

Gnomad4 ASJ exome AF: 0.293

Gnomad4 EAS exome AF: 0.601

Gnomad4 SAS exome AF: 0.282

Gnomad4 FIN exome AF: 0.287

Gnomad4 NFE exome AF: 0.310

Gnomad4 OTH exome AF: 0.315

GnomAD4 genome AF: 0.292 AC: 44136 AN: 151250 Hom.: 6846 Cov.: 31 AF XY: 0.293 AC XY: 21643 AN XY: 73870

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.320

Alfa AF: 0.300 Hom.: 2207

Bravo AF: 0.294

ESP6500AA AF: 0.192 AC: 782

ESP6500EA AF: 0.298 AC: 2471

ExAC AF: 0.320 AC: 38643

EpiCase AF: 0.310

EpiControl AF: 0.313

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	Nov 12, 2018	- -

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	0.096
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.9
DANN	Benign	0.71
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0090	N
LIST_S2	Benign	0.68	T
MetaRNN	Benign	0.000037	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.044
Sift	Uncertain	0.026	D
Vest4		0.032
ClinPred		0.0053	T
GERP RS		-3.5
Varity_R		0.019
gMVP		0.27

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: rs60268710; hg19: chr11-1267562; COSMIC: COSV101499941;