11-1226967-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002458.3(MUC5B):c.462-64G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 1,517,360 control chromosomes in the GnomAD database, including 306,158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.63 (28803 hom., cov: 30)
  • Exomes 𝑓: 0.63 (277355 hom.)
• Consequence: MUC5B NM_002458.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.69

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 11-1226967-G-T is Benign according to our data. Variant chr11-1226967-G-T is described in ClinVar as [Benign]. Clinvar id is 1282609.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3	c.462-64G>T		intron_variant		ENST00000529681.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5	c.462-64G>T		intron_variant		5	NM_002458.3	P1
MUC5B	ENST00000525715.5	n.520-64G>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.631 AC: 92643 AN: 146742 Hom.: 28771 Cov.: 30

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.590

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.635

GnomAD4 exome AF: 0.634 AC: 869176 AN: 1370510 Hom.: 277355 Cov.: 23 AF XY: 0.632 AC XY: 428298 AN XY: 677586

Gnomad4 AFR exome AF: 0.628

Gnomad4 AMR exome AF: 0.784

Gnomad4 ASJ exome AF: 0.583

Gnomad4 EAS exome AF: 0.595

Gnomad4 SAS exome AF: 0.581

Gnomad4 FIN exome AF: 0.676

Gnomad4 NFE exome AF: 0.634

Gnomad4 OTH exome AF: 0.634

GnomAD4 genome AF: 0.631 AC: 92721 AN: 146850 Hom.: 28803 Cov.: 30 AF XY: 0.635 AC XY: 45480 AN XY: 71676

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.709

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.593

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.670

Gnomad4 NFE AF: 0.622

Gnomad4 OTH AF: 0.636

Alfa AF: 0.609 Hom.: 2945

Asia WGS AF: 0.566 AC: 1965 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	0.0020
Dann	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs908224; hg19: chr11-1248197; COSMIC: COSV71592710; COSMIC: COSV71592710;