rs139052978

chr11-1245928-G-Achr11-1245928-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_002458.3(MUC5B):c.9048G>A(p.Pro3016=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 1,608,322 control chromosomes in the GnomAD database, including 599 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (38 hom., cov: 29)
  • Exomes 𝑓: 0.023 (561 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.67

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 11-1245928-G-A is Benign according to our data. Variant chr11-1245928-G-A is described in ClinVar as [Benign]. Clinvar id is 403149.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.66 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0179 (2633/147404) while in subpopulation NFE AF= 0.0268 (1782/66530). AF 95% confidence interval is 0.0257. There are 38 homozygotes in gnomad4. There are 1286 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd at 2633 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3	c.9048G>A	p.Pro3016=	synonymous_variant	31/49	ENST00000529681.5
MUC5B-AS1	NR_157183.1	n.57-3290C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5	c.9048G>A	p.Pro3016=	synonymous_variant	31/49	5	NM_002458.3	P1
MUC5B-AS1	ENST00000532061.2	n.57-3290C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0179 AC: 2633 AN: 147280 Hom.: 38 Cov.: 29

Gnomad AFR AF: 0.00423

Gnomad AMI AF: 0.00336

Gnomad AMR AF: 0.0144

Gnomad ASJ AF: 0.00857

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00886

Gnomad FIN AF: 0.0355

Gnomad MID AF: 0.0219

Gnomad NFE AF: 0.0268

Gnomad OTH AF: 0.0155

GnomAD3 exomes AF: 0.0176 AC: 4393 AN: 248956 Hom.: 82 AF XY: 0.0180 AC XY: 2430 AN XY: 135050

Gnomad AFR exome AF: 0.00342

Gnomad AMR exome AF: 0.00762

Gnomad ASJ exome AF: 0.0110

Gnomad EAS exome AF: 0.0000556

Gnomad SAS exome AF: 0.00759

Gnomad FIN exome AF: 0.0330

Gnomad NFE exome AF: 0.0258

Gnomad OTH exome AF: 0.0180

GnomAD4 exome AF: 0.0235 AC: 34275 AN: 1460918 Hom.: 561 Cov.: 70 AF XY: 0.0230 AC XY: 16696 AN XY: 726756

Gnomad4 AFR exome AF: 0.00413

Gnomad4 AMR exome AF: 0.00821

Gnomad4 ASJ exome AF: 0.0114

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00754

Gnomad4 FIN exome AF: 0.0308

Gnomad4 NFE exome AF: 0.0268

Gnomad4 OTH exome AF: 0.0218

GnomAD4 genome AF: 0.0179 AC: 2633 AN: 147404 Hom.: 38 Cov.: 29 AF XY: 0.0179 AC XY: 1286 AN XY: 71798

Gnomad4 AFR AF: 0.00421

Gnomad4 AMR AF: 0.0144

Gnomad4 ASJ AF: 0.00857

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00887

Gnomad4 FIN AF: 0.0355

Gnomad4 NFE AF: 0.0268

Gnomad4 OTH AF: 0.0154

Alfa AF: 0.0168 Hom.: 10

Bravo AF: 0.0151

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.0243

EpiControl AF: 0.0250

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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: Silent variant not in splice consensus -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	4.9
Dann	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs139052978; hg19: chr11-1267158; COSMIC: COSV71591237;