rs140245340

chr11-1239789-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002458.3(MUC5B):c.3584-10C>T 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 0.000364 in 1,606,524 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00036 (2 hom.)
• Consequence: MUC5B NM_002458.3 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00009451
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.199

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-1239789-C-T is Benign according to our data. Variant chr11-1239789-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 504732.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 55 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3	c.3584-10C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000529681.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5	c.3584-10C>T		splice_polypyrimidine_tract_variant, intron_variant		5	NM_002458.3	P1

Frequencies

GnomAD3 genomes AF: 0.000361 AC: 55 AN: 152196 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000850

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.000581 AC: 137 AN: 235970 Hom.: 0 AF XY: 0.000607 AC XY: 78 AN XY: 128416

Gnomad AFR exome AF: 0.0000718

Gnomad AMR exome AF: 0.000805

Gnomad ASJ exome AF: 0.00135

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00179

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000282

Gnomad OTH exome AF: 0.00244

GnomAD4 exome AF: 0.000364 AC: 530 AN: 1454210 Hom.: 2 Cov.: 33 AF XY: 0.000436 AC XY: 315 AN XY: 722720

Gnomad4 AFR exome AF: 0.000450

Gnomad4 AMR exome AF: 0.000750

Gnomad4 ASJ exome AF: 0.00108

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00192

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000178

Gnomad4 OTH exome AF: 0.000682

GnomAD4 genome AF: 0.000361 AC: 55 AN: 152314 Hom.: 0 Cov.: 33 AF XY: 0.000336 AC XY: 25 AN XY: 74476

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.000849

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000616 Hom.: 0

Bravo AF: 0.000385

Asia WGS AF: 0.00202 AC: 7 AN: 3478

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

May 15, 2017

c.3584-10C>T in intron 27 of MUC5B: This variant is not expected to have clinica l significance because a C>T change at this position does not diverge from the s plice consensus sequence and is therefore unlikely to impact splicing. It has be en identified in 0.2% (53/29256) of South Asian chromosomes by the Genome Aggreg ation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs140245340). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.5
Dann	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000095
dbscSNV1_RF	Benign	0.010
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: rs140245340; hg19: chr11-1261019;