chr11-1233859-CCCCTG-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• interstitial lung disease

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002458.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	NM_002458.3	MANE Select	c.2377+30_2377+34delTGCCC		intron	N/A	NP_002449.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.2377+12_2377+16delCCCTG		intron	N/A	ENSP00000436812.1
	MUC5B	ENST00000525715.5	TSL:1	n.2435+12_2435+16delCCCTG		intron	N/A

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

GnomAD2 exomes AF: 0.442 AC: 80149 AN: 181460 AF XY: 0.434

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 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

African (AFR) AF: 0.289 AC: 9404 AN: 32578

American (AMR) AF: 0.561 AC: 21638 AN: 38558

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 10771 AN: 25490

East Asian (EAS) AF: 0.693 AC: 25780 AN: 37176

South Asian (SAS) AF: 0.417 AC: 34028 AN: 81628

European-Finnish (FIN) AF: 0.483 AC: 23420 AN: 48462

Middle Eastern (MID) AF: 0.399 AC: 1874 AN: 4698

European-Non Finnish (NFE) AF: 0.430 AC: 467964 AN: 1089358

Other (OTH) AF: 0.435 AC: 25535 AN: 58730

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

African (AFR) AF: 0.303 AC: 12494 AN: 41274

American (AMR) AF: 0.536 AC: 8147 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1531 AN: 3468

East Asian (EAS) AF: 0.654 AC: 3290 AN: 5034

South Asian (SAS) AF: 0.430 AC: 2058 AN: 4782

European-Finnish (FIN) AF: 0.505 AC: 5264 AN: 10424

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.436 AC: 29423 AN: 67540

Other (OTH) AF: 0.442 AC: 927 AN: 2096

Alfa AF: 0.335 Hom.: 1356

Asia WGS AF: 0.561 AC: 1946 AN: 3472

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs55859402; hg19: chr11-1255089;