rs139960671

chr11-1245369-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.8489C>T(p.Pro2830Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,568,878 control chromosomes in the GnomAD database, including 54,294 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 0.14 (3022 hom., cov: 21)
  • Exomes 𝑓: 0.19 (51272 hom.)
• Consequence: MUC5B NM_002458.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.74

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=0.0060741007).
• BP6: Variant 11-1245369-C-T is Benign according to our data. Variant chr11-1245369-C-T is described in ClinVar as [Benign]. Clinvar id is 403146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3	c.8489C>T	p.Pro2830Leu	missense_variant	31/49	ENST00000529681.5
MUC5B-AS1	NR_157183.1	n.57-2731G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5	c.8489C>T	p.Pro2830Leu	missense_variant	31/49	5	NM_002458.3	P1
MUC5B-AS1	ENST00000532061.2	n.57-2731G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.139 AC: 19212 AN: 137856 Hom.: 3019 Cov.: 21

Gnomad AFR AF: 0.0353

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.00502

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.132

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.137

GnomAD3 exomes AF: 0.166 AC: 39772 AN: 239792 Hom.: 8763 AF XY: 0.173 AC XY: 22584 AN XY: 130556

Gnomad AFR exome AF: 0.0328

Gnomad AMR exome AF: 0.101

Gnomad ASJ exome AF: 0.177

Gnomad EAS exome AF: 0.00329

Gnomad SAS exome AF: 0.173

Gnomad FIN exome AF: 0.273

Gnomad NFE exome AF: 0.207

Gnomad OTH exome AF: 0.176

GnomAD4 exome AF: 0.191 AC: 272927 AN: 1430906 Hom.: 51272 Cov.: 106 AF XY: 0.191 AC XY: 135906 AN XY: 712088

Gnomad4 AFR exome AF: 0.0300

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.168

Gnomad4 EAS exome AF: 0.00198

Gnomad4 SAS exome AF: 0.165

Gnomad4 FIN exome AF: 0.233

Gnomad4 NFE exome AF: 0.207

Gnomad4 OTH exome AF: 0.179

GnomAD4 genome AF: 0.139 AC: 19216 AN: 137972 Hom.: 3022 Cov.: 21 AF XY: 0.141 AC XY: 9392 AN XY: 66548

Gnomad4 AFR AF: 0.0351

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.00503

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.139

Alfa AF: 0.163 Hom.: 762

ESP6500AA AF: 0.0401 AC: 162

ESP6500EA AF: 0.209 AC: 1706

ExAC AF: 0.166 AC: 19621

Asia WGS AF: 0.0740 AC: 256 AN: 3456

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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 -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.069
Dann	Benign	0.85
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.40	T
MetaRNN	Benign	0.0061	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.0080
Sift	Benign	0.058	T
Vest4		0.011
ClinPred		0.00065	T
GERP RS		-0.90
Varity_R		0.028
gMVP		0.42

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: rs139960671; hg19: chr11-1266599; COSMIC: COSV71589889;