rs367905040

chr11-1248793-T-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.11913T>C(p.Pro3971=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0301 in 1,532,500 control chromosomes in the GnomAD database, including 959 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.028 (64 hom., cov: 26)
  • Exomes 𝑓: 0.030 (895 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.19

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=-0.96).
• BP6: Variant 11-1248793-T-C is Benign according to our data. Variant chr11-1248793-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 403190.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.19 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0282 (3776/133790) while in subpopulation NFE AF= 0.0358 (2218/61986). AF 95% confidence interval is 0.0345. There are 64 homozygotes in gnomad4. There are 1879 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 3777 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3	c.11913T>C	p.Pro3971=	synonymous_variant	31/49	ENST00000529681.5
MUC5B-AS1	NR_157183.1	n.56+828A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5	c.11913T>C	p.Pro3971=	synonymous_variant	31/49	5	NM_002458.3	P1
MUC5B-AS1	ENST00000532061.2	n.56+828A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0283 AC: 3777 AN: 133662 Hom.: 64 Cov.: 26

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.00129

Gnomad AMR AF: 0.00826

Gnomad ASJ AF: 0.0308

Gnomad EAS AF: 0.000229

Gnomad SAS AF: 0.00988

Gnomad FIN AF: 0.0796

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0358

Gnomad OTH AF: 0.0258

GnomAD3 exomes AF: 0.0250 AC: 3819 AN: 152744 Hom.: 90 AF XY: 0.0245 AC XY: 1982 AN XY: 80974

Gnomad AFR exome AF: 0.0133

Gnomad AMR exome AF: 0.00540

Gnomad ASJ exome AF: 0.0282

Gnomad EAS exome AF: 0.0000913

Gnomad SAS exome AF: 0.00994

Gnomad FIN exome AF: 0.0732

Gnomad NFE exome AF: 0.0325

Gnomad OTH exome AF: 0.0229

GnomAD4 exome AF: 0.0303 AC: 42349 AN: 1398710 Hom.: 895 Cov.: 52 AF XY: 0.0296 AC XY: 20419 AN XY: 689964

Gnomad4 AFR exome AF: 0.0118

Gnomad4 AMR exome AF: 0.00613

Gnomad4 ASJ exome AF: 0.0291

Gnomad4 EAS exome AF: 0.0000560

Gnomad4 SAS exome AF: 0.00974

Gnomad4 FIN exome AF: 0.0726

Gnomad4 NFE exome AF: 0.0326

Gnomad4 OTH exome AF: 0.0264

GnomAD4 genome AF: 0.0282 AC: 3776 AN: 133790 Hom.: 64 Cov.: 26 AF XY: 0.0289 AC XY: 1879 AN XY: 64958

Gnomad4 AFR AF: 0.0152

Gnomad4 AMR AF: 0.00825

Gnomad4 ASJ AF: 0.0308

Gnomad4 EAS AF: 0.000230

Gnomad4 SAS AF: 0.00988

Gnomad4 FIN AF: 0.0796

Gnomad4 NFE AF: 0.0358

Gnomad4 OTH AF: 0.0255

Alfa AF: 0.0315 Hom.: 21

Bravo AF: 0.0207

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
BayesDel_noAF	Benign	-0.96
Cadd	Benign	2.6
Dann	Benign	0.46

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: rs367905040; hg19: chr11-1270023;