rs201236828

Positions:

• chr11-1246020-C-A
• chr11-1246020-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002458.3(MUC5B):​c.9140C>A​(p.Thr3047Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.022 in 1,590,254 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (0 hom., cov: 29)
  • Exomes 𝑓: 0.022 (0 hom.)
• Consequence: MUC5B NM_002458.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.239

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0032743812).
• BP6: Variant 11-1246020-C-A is Benign according to our data. Variant chr11-1246020-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 403186.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0194 (2923/150452) while in subpopulation NFE AF= 0.0278 (1868/67290). AF 95% confidence interval is 0.0267. There are 0 homozygotes in gnomad4. There are 1445 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2923 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3	c.9140C>A	p.Thr3047Asn	missense_variant	31/49	ENST00000529681.5
MUC5B-AS1	NR_157183.1	n.57-3382G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5	c.9140C>A	p.Thr3047Asn	missense_variant	31/49	5	NM_002458.3	P1
MUC5B-AS1	ENST00000532061.2	n.57-3382G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0194 AC: 2923 AN: 150334 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00539

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00547

Gnomad ASJ AF: 0.0250

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00648

Gnomad FIN AF: 0.0579

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0278

Gnomad OTH AF: 0.0155

GnomAD3 exomes AF: 0.0224 AC: 5542 AN: 247340 Hom.: 0 AF XY: 0.0222 AC XY: 2973 AN XY: 134206

Gnomad AFR exome AF: 0.00554

Gnomad AMR exome AF: 0.00432

Gnomad ASJ exome AF: 0.0227

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00745

Gnomad FIN exome AF: 0.0658

Gnomad NFE exome AF: 0.0296

Gnomad OTH exome AF: 0.0245

GnomAD4 exome AF: 0.0222 AC: 31999 AN: 1439802 Hom.: 0 Cov.: 80 AF XY: 0.0220 AC XY: 15786 AN XY: 716818

Gnomad4 AFR exome AF: 0.00307

Gnomad4 AMR exome AF: 0.00435

Gnomad4 ASJ exome AF: 0.0233

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00751

Gnomad4 FIN exome AF: 0.0651

Gnomad4 NFE exome AF: 0.0236

Gnomad4 OTH exome AF: 0.0211

GnomAD4 genome AF: 0.0194 AC: 2923 AN: 150452 Hom.: 0 Cov.: 29 AF XY: 0.0197 AC XY: 1445 AN XY: 73482

Gnomad4 AFR AF: 0.00537

Gnomad4 AMR AF: 0.00546

Gnomad4 ASJ AF: 0.0250

Gnomad4 EAS AF: 0.000196

Gnomad4 SAS AF: 0.00649

Gnomad4 FIN AF: 0.0579

Gnomad4 NFE AF: 0.0278

Gnomad4 OTH AF: 0.0153

Alfa AF: 0.0246 Hom.: 0

ESP6500AA AF: 0.00428 AC: 18

ESP6500EA AF: 0.0199 AC: 167

ExAC AF: 0.0267 AC: 3238

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely 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	0.12
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.63
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.39	T
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.10
Sift	Benign	0.12	T
Vest4		0.045
ClinPred		0.012	T
GERP RS		2.8
Varity_R		0.054
gMVP		0.22

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: rs201236828; hg19: chr11-1267250; COSMIC: COSV71594262;