11-1243512-G-C

Position:

• chr11-1243512-G-C

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.6632G>C​(p.Arg2211Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 1,433,604 control chromosomes in the GnomAD database, including 176,584 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 0.38 (9470 hom., cov: 20)
  • Exomes 𝑓: 0.47 (167114 hom.)
• Consequence: MUC5B NM_002458.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.670

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=4.529953E-4).
• BP6: Variant 11-1243512-G-C is Benign according to our data. Variant chr11-1243512-G-C is described in ClinVar as [Benign]. Clinvar id is 403139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.6632G>C	p.Arg2211Pro	missense_variant	31/49	ENST00000529681.5	NP_002449.2
MUC5B-AS1	NR_157183.1	n.57-874C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.6632G>C	p.Arg2211Pro	missense_variant	31/49	5	NM_002458.3	ENSP00000436812.1
MUC5B-AS1	ENST00000532061.2	n.57-874C>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.375 AC: 43160 AN: 115034 Hom.: 9453 Cov.: 20

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.472

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.377

GnomAD3 exomes AF: 0.409 AC: 88330 AN: 216070 Hom.: 14727 AF XY: 0.405 AC XY: 47595 AN XY: 117546

Gnomad AFR exome AF: 0.277

Gnomad AMR exome AF: 0.460

Gnomad ASJ exome AF: 0.365

Gnomad EAS exome AF: 0.634

Gnomad SAS exome AF: 0.364

Gnomad FIN exome AF: 0.421

Gnomad NFE exome AF: 0.387

Gnomad OTH exome AF: 0.405

GnomAD4 exome AF: 0.469 AC: 618418 AN: 1318450 Hom.: 167114 Cov.: 116 AF XY: 0.466 AC XY: 306146 AN XY: 656660

Gnomad4 AFR exome AF: 0.319

Gnomad4 AMR exome AF: 0.589

Gnomad4 ASJ exome AF: 0.440

Gnomad4 EAS exome AF: 0.709

Gnomad4 SAS exome AF: 0.427

Gnomad4 FIN exome AF: 0.551

Gnomad4 NFE exome AF: 0.460

Gnomad4 OTH exome AF: 0.462

GnomAD4 genome AF: 0.375 AC: 43209 AN: 115154 Hom.: 9470 Cov.: 20 AF XY: 0.383 AC XY: 21317 AN XY: 55708

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.385

Alfa AF: 0.311 Hom.: 1010

ExAC AF: 0.408 AC: 49352

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	0.062
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.0
DANN	Benign	0.50
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00017	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.00045	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.81	N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.61	N
REVEL	Benign	0.047
Sift	Benign	0.17	T
Vest4		0.023
ClinPred		0.00058	T
GERP RS		1.8
Varity_R		0.099
gMVP		0.28

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: rs137973688; hg19: chr11-1264742; COSMIC: COSV71589895; COSMIC: COSV71589895;