11-1230071-C-T

Variant names:

• chr11-1230071-C-T
• rs2672810
• NM_002458.3:c.1287C>T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002458.3(MUC5B):​c.1287C>T​(p.Gly429Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0293 in 1,611,972 control chromosomes in the GnomAD database, including 897 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 (840 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.80

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 11-1230071-C-T is Benign according to our data. Variant chr11-1230071-C-T is described in ClinVar as [Benign]. Clinvar id is 178788.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.8 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0228 (3479/152278) while in subpopulation NFE AF= 0.0328 (2227/67990). AF 95% confidence interval is 0.0316. There are 57 homozygotes in gnomad4. There are 1735 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3479 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.1287C>T	p.Gly429Gly	synonymous_variant	Exon 11 of 49	ENST00000529681.5	NP_002449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.1287C>T	p.Gly429Gly	synonymous_variant	Exon 11 of 49	5	NM_002458.3	ENSP00000436812.1
MUC5B	ENST00000525715.5	n.1345C>T		non_coding_transcript_exon_variant	Exon 11 of 26	1

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 3479 AN: 152160 Hom.: 57 Cov.: 34

Gnomad AFR AF: 0.00555

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00674

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00807

Gnomad FIN AF: 0.0694

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0328

Gnomad OTH AF: 0.0201

GnomAD3 exomes AF: 0.0260 AC: 6441 AN: 247508 Hom.: 138 AF XY: 0.0259 AC XY: 3491 AN XY: 134534

Gnomad AFR exome AF: 0.00642

Gnomad AMR exome AF: 0.00483

Gnomad ASJ exome AF: 0.0286

Gnomad EAS exome AF: 0.0000557

Gnomad SAS exome AF: 0.00941

Gnomad FIN exome AF: 0.0744

Gnomad NFE exome AF: 0.0344

Gnomad OTH exome AF: 0.0278

GnomAD4 exome AF: 0.0300 AC: 43718 AN: 1459694 Hom.: 840 Cov.: 33 AF XY: 0.0293 AC XY: 21294 AN XY: 726134

Gnomad4 AFR exome AF: 0.00388

Gnomad4 AMR exome AF: 0.00527

Gnomad4 ASJ exome AF: 0.0292

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00951

Gnomad4 FIN exome AF: 0.0729

Gnomad4 NFE exome AF: 0.0327

Gnomad4 OTH exome AF: 0.0270

GnomAD4 genome AF: 0.0228 AC: 3479 AN: 152278 Hom.: 57 Cov.: 34 AF XY: 0.0233 AC XY: 1735 AN XY: 74466

Gnomad4 AFR AF: 0.00553

Gnomad4 AMR AF: 0.00673

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00808

Gnomad4 FIN AF: 0.0694

Gnomad4 NFE AF: 0.0328

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.0285 Hom.: 35

Bravo AF: 0.0173

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.0252

EpiControl AF: 0.0264

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Gly429Gly in exon 11 of MUC5B: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 3.3% (271/8284) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2672810). -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.44
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2672810; hg19: chr11-1251301; COSMIC: COSV101500457; COSMIC: COSV101500457;