11-1248442-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002458.3(MUC5B):c.11562T>C(p.Ser3854=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 1,551,570 control chromosomes in the GnomAD database, including 213,466 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19263 hom., cov: 27)
  • Exomes 𝑓: 0.50 (194203 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -6.02

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP6: Variant 11-1248442-T-C is Benign according to our data. Variant chr11-1248442-T-C is described in ClinVar as [Benign]. Clinvar id is 403169.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-6.02 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3	c.11562T>C	p.Ser3854=	synonymous_variant	31/49	ENST00000529681.5
MUC5B-AS1	NR_157183.1	n.56+1179A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5	c.11562T>C	p.Ser3854=	synonymous_variant	31/49	5	NM_002458.3	P1
MUC5B-AS1	ENST00000532061.2	n.56+1179A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.504 AC: 73405 AN: 145568 Hom.: 19241 Cov.: 27

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.523

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.518

GnomAD3 exomes AF: 0.519 AC: 118570 AN: 228508 Hom.: 35538 AF XY: 0.513 AC XY: 63642 AN XY: 123946

Gnomad AFR exome AF: 0.413

Gnomad AMR exome AF: 0.622

Gnomad ASJ exome AF: 0.519

Gnomad EAS exome AF: 0.666

Gnomad SAS exome AF: 0.491

Gnomad FIN exome AF: 0.540

Gnomad NFE exome AF: 0.481

Gnomad OTH exome AF: 0.515

GnomAD4 exome AF: 0.501 AC: 703882 AN: 1405874 Hom.: 194203 Cov.: 117 AF XY: 0.500 AC XY: 349950 AN XY: 699894

Gnomad4 AFR exome AF: 0.439

Gnomad4 AMR exome AF: 0.613

Gnomad4 ASJ exome AF: 0.523

Gnomad4 EAS exome AF: 0.707

Gnomad4 SAS exome AF: 0.501

Gnomad4 FIN exome AF: 0.550

Gnomad4 NFE exome AF: 0.487

Gnomad4 OTH exome AF: 0.503

GnomAD4 genome AF: 0.504 AC: 73473 AN: 145696 Hom.: 19263 Cov.: 27 AF XY: 0.510 AC XY: 36214 AN XY: 70988

Gnomad4 AFR AF: 0.450

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.496

Gnomad4 OTH AF: 0.521

Alfa AF: 0.493 Hom.: 3598

Bravo AF: 0.502

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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.3
Dann	Benign	0.55

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: rs4963057; hg19: chr11-1269672; COSMIC: COSV71590604;