NM_002458.3:c.2377+30_2377+34delTGCCC

Variant names:

• chr11-1233859-CCCCTG-C
• rs55859402
• NM_002458.3:c.2377+30_2377+34delTGCCC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002458.3(MUC5B):​c.2377+30_2377+34delTGCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 1,567,680 control chromosomes in the GnomAD database, including 154,485 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (14045 hom., cov: 0)
  • Exomes 𝑓: 0.44 (140440 hom.)
• Consequence: MUC5B NM_002458.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.02

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 11-1233859-CCCCTG-C is Benign according to our data. Variant chr11-1233859-CCCCTG-C is described in ClinVar as [Benign]. Clinvar id is 403127.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.2377+30_2377+34delTGCCC		intron_variant	Intron 19 of 48	ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.2377+12_2377+16delCCCTG		intron_variant	Intron 19 of 48	5	NM_002458.3	ENSP00000436812.1
MUC5B	ENST00000525715.5	n.2435+12_2435+16delCCCTG		intron_variant	Intron 19 of 25	1

Frequencies

GnomAD3 genomes AF: 0.422 AC: 63675 AN: 150886 Hom.: 14027 Cov.: 0

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.437

GnomAD3 exomes AF: 0.442 AC: 80149 AN: 181460 Hom.: 19525 AF XY: 0.434 AC XY: 42426 AN XY: 97810

Gnomad AFR exome AF: 0.254

Gnomad AMR exome AF: 0.571

Gnomad ASJ exome AF: 0.419

Gnomad EAS exome AF: 0.641

Gnomad SAS exome AF: 0.404

Gnomad FIN exome AF: 0.469

Gnomad NFE exome AF: 0.398

Gnomad OTH exome AF: 0.445

GnomAD4 exome AF: 0.438 AC: 620414 AN: 1416678 Hom.: 140440 AF XY: 0.437 AC XY: 306345 AN XY: 701694

Gnomad4 AFR exome AF: 0.289

Gnomad4 AMR exome AF: 0.561

Gnomad4 ASJ exome AF: 0.423

Gnomad4 EAS exome AF: 0.693

Gnomad4 SAS exome AF: 0.417

Gnomad4 FIN exome AF: 0.483

Gnomad4 NFE exome AF: 0.430

Gnomad4 OTH exome AF: 0.435

GnomAD4 genome AF: 0.422 AC: 63721 AN: 151002 Hom.: 14045 Cov.: 0 AF XY: 0.430 AC XY: 31707 AN XY: 73738

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.654

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.442

Asia WGS AF: 0.561 AC: 1946 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs55859402; hg19: chr11-1255089;