11-1228306-G-T

Variant names:

• chr11-1228306-G-T
• rs4963050
• NM_002458.3:c.775-258G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002458.3(MUC5B):​c.775-258G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,074 control chromosomes in the GnomAD database, including 7,197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.30 (7197 hom., cov: 34)
• Consequence: MUC5B NM_002458.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.894
• Publications: 7 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 11-1228306-G-T is Benign according to our data. Variant chr11-1228306-G-T is described in ClinVar as Benign. ClinVar VariationId is 1243572.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.775-258G>T		intron_variant	Intron 7 of 48	ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.775-258G>T		intron_variant	Intron 7 of 48	5	NM_002458.3	ENSP00000436812.1
MUC5B	ENST00000525715.5	n.833-258G>T		intron_variant	Intron 7 of 25	1
MUC5B	ENST00000531082.1	n.-214G>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45481 AN: 151958 Hom.: 7180 Cov.: 34

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.322

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.299 AC: 45531 AN: 152074 Hom.: 7197 Cov.: 34 AF XY: 0.301 AC XY: 22347 AN XY: 74342

African (AFR) AF: 0.236 AC: 9816 AN: 41516

American (AMR) AF: 0.335 AC: 5115 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1054 AN: 3468

East Asian (EAS) AF: 0.597 AC: 3069 AN: 5138

South Asian (SAS) AF: 0.289 AC: 1390 AN: 4816

European-Finnish (FIN) AF: 0.280 AC: 2967 AN: 10592

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.309 AC: 21023 AN: 67944

Other (OTH) AF: 0.329 AC: 696 AN: 2114

Alfa AF: 0.155 Hom.: 304

Bravo AF: 0.302

Asia WGS AF: 0.486 AC: 1686 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.73
PhyloP100		-0.89
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4963050; hg19: chr11-1249536;