rs371299435

Positions:

• chr11-1245589-G-A
• chr11-1245589-G-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_002458.3(MUC5B):​c.8709G>A​(p.Ala2903=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,581,756 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 26)
  • Exomes 𝑓: 0.0026 (47 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -12.0

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 11-1245589-G-A is Benign according to our data. Variant chr11-1245589-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 403182.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-12 with no splicing effect.
• BS2: High AC in GnomAd4 at 222 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.8709G>A	p.Ala2903=	synonymous_variant	31/49	ENST00000529681.5	NP_002449.2
MUC5B-AS1	NR_157183.1	n.57-2951C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.8709G>A	p.Ala2903=	synonymous_variant	31/49	5	NM_002458.3	ENSP00000436812	P1
MUC5B-AS1	ENST00000532061.2	n.57-2951C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00151 AC: 222 AN: 146550 Hom.: 1 Cov.: 26

Gnomad AFR AF: 0.000765

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000344

Gnomad ASJ AF: 0.00410

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000227

Gnomad FIN AF: 0.000200

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00250

Gnomad OTH AF: 0.00152

GnomAD3 exomes AF: 0.00155 AC: 293 AN: 189424 Hom.: 4 AF XY: 0.00164 AC XY: 170 AN XY: 103882

Gnomad AFR exome AF: 0.000843

Gnomad AMR exome AF: 0.000628

Gnomad ASJ exome AF: 0.00325

Gnomad EAS exome AF: 0.0000729

Gnomad SAS exome AF: 0.0000384

Gnomad FIN exome AF: 0.000178

Gnomad NFE exome AF: 0.00281

Gnomad OTH exome AF: 0.00101

GnomAD4 exome AF: 0.00264 AC: 3785 AN: 1435090 Hom.: 47 Cov.: 41 AF XY: 0.00253 AC XY: 1803 AN XY: 712682

Gnomad4 AFR exome AF: 0.000640

Gnomad4 AMR exome AF: 0.000674

Gnomad4 ASJ exome AF: 0.00470

Gnomad4 EAS exome AF: 0.0000513

Gnomad4 SAS exome AF: 0.0000236

Gnomad4 FIN exome AF: 0.000235

Gnomad4 NFE exome AF: 0.00316

Gnomad4 OTH exome AF: 0.00228

GnomAD4 genome AF: 0.00151 AC: 222 AN: 146666 Hom.: 1 Cov.: 26 AF XY: 0.00111 AC XY: 79 AN XY: 71306

Gnomad4 AFR AF: 0.000763

Gnomad4 AMR AF: 0.000343

Gnomad4 ASJ AF: 0.00410

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000227

Gnomad4 FIN AF: 0.000200

Gnomad4 NFE AF: 0.00250

Gnomad4 OTH AF: 0.00151

Alfa AF: 0.00138 Hom.: 0

Bravo AF: 0.00151

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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: Silent variant not near splice site -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

MUC5B: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	7.3
DANN	Benign	0.74

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: rs371299435; hg19: chr11-1266819;