11-1229679-G-C

Position:

• chr11-1229679-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002458.3(MUC5B):​c.1103-11G>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0289 in 1,552,274 control chromosomes in the GnomAD database, including 831 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (57 hom., cov: 34)
  • Exomes 𝑓: 0.030 (774 hom.)
• Consequence: MUC5B NM_002458.3 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001679
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.18

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 11-1229679-G-C is Benign according to our data. Variant chr11-1229679-G-C is described in ClinVar as [Benign]. Clinvar id is 178787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0228 (3477/152266) while in subpopulation NFE AF= 0.0327 (2221/67988). AF 95% confidence interval is 0.0315. There are 57 homozygotes in gnomad4. There are 1736 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3477 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.1103-11G>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.1103-11G>C		splice_polypyrimidine_tract_variant, intron_variant		5	NM_002458.3	ENSP00000436812	P1
MUC5B	ENST00000525715.5	n.1161-11G>C		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		1
MUC5B	ENST00000531082.1	n.373-11G>C		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 3477 AN: 152148 Hom.: 57 Cov.: 34

Gnomad AFR AF: 0.00557

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00680

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00848

Gnomad FIN AF: 0.0694

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0327

Gnomad OTH AF: 0.0201

GnomAD3 exomes AF: 0.0228 AC: 3655 AN: 160586 Hom.: 69 AF XY: 0.0225 AC XY: 1969 AN XY: 87594

Gnomad AFR exome AF: 0.00542

Gnomad AMR exome AF: 0.00492

Gnomad ASJ exome AF: 0.0275

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00974

Gnomad FIN exome AF: 0.0695

Gnomad NFE exome AF: 0.0335

Gnomad OTH exome AF: 0.0230

GnomAD4 exome AF: 0.0296 AC: 41459 AN: 1400008 Hom.: 774 Cov.: 32 AF XY: 0.0290 AC XY: 20059 AN XY: 692098

Gnomad4 AFR exome AF: 0.00392

Gnomad4 AMR exome AF: 0.00542

Gnomad4 ASJ exome AF: 0.0289

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00987

Gnomad4 FIN exome AF: 0.0708

Gnomad4 NFE exome AF: 0.0325

Gnomad4 OTH exome AF: 0.0262

GnomAD4 genome AF: 0.0228 AC: 3477 AN: 152266 Hom.: 57 Cov.: 34 AF XY: 0.0233 AC XY: 1736 AN XY: 74446

Gnomad4 AFR AF: 0.00556

Gnomad4 AMR AF: 0.00680

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00849

Gnomad4 FIN AF: 0.0694

Gnomad4 NFE AF: 0.0327

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.0188 Hom.: 12

Bravo AF: 0.0172

Asia WGS AF: 0.00260 AC: 9 AN: 3478

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

Feb 21, 2013

1103-11G>C in intron 9 of MUC5B: This variant is not expected to have clinical s ignificance because it has been identified in 2.7% (225/8288) of European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs56069229). -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.54
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000017
dbscSNV1_RF	Benign	0.0
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: rs56069229; hg19: chr11-1250909;