chr11-1230071-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 57 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002458.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	NM_002458.3	MANE Select	c.1287C>T	p.Gly429Gly	synonymous	Exon 11 of 49	NP_002449.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.1287C>T	p.Gly429Gly	synonymous	Exon 11 of 49	ENSP00000436812.1
	MUC5B	ENST00000525715.5	TSL:1	n.1345C>T		non_coding_transcript_exon	Exon 11 of 26

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

GnomAD2 exomes AF: 0.0260 AC: 6441 AN: 247508 AF XY: 0.0259

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 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

African (AFR) AF: 0.00388 AC: 130 AN: 33466

American (AMR) AF: 0.00527 AC: 235 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.0292 AC: 761 AN: 26080

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.00951 AC: 819 AN: 86148

European-Finnish (FIN) AF: 0.0729 AC: 3800 AN: 52144

Middle Eastern (MID) AF: 0.00451 AC: 26 AN: 5762

European-Non Finnish (NFE) AF: 0.0327 AC: 36314 AN: 1111470

Other (OTH) AF: 0.0270 AC: 1631 AN: 60302

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

African (AFR) AF: 0.00553 AC: 230 AN: 41570

American (AMR) AF: 0.00673 AC: 103 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00808 AC: 39 AN: 4828

European-Finnish (FIN) AF: 0.0694 AC: 737 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0328 AC: 2227 AN: 67990

Other (OTH) AF: 0.0199 AC: 42 AN: 2110

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.44
DANN	Benign	0.56
PhyloP100		-5.8
Mutation Taster		=90/10	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2672810; hg19: chr11-1251301; COSMIC: COSV101500457; COSMIC: COSV101500457;