NM_002458.3:c.3834C>T

Variant names:

• chr11-1240239-C-T
• rs55913363
• NM_002458.3:c.3834C>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.3834C>T​(p.Thr1278Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00247 in 1,613,558 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (41 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (42 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.31
• Publications: 0 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=-0.78).
• BP6: Variant 11-1240239-C-T is Benign according to our data. Variant chr11-1240239-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 504733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.31 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.012 (1831/152326) while in subpopulation AFR AF = 0.0402 (1670/41562). AF 95% confidence interval is 0.0386. There are 41 homozygotes in GnomAd4. There are 873 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 41 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.3834C>T	p.Thr1278Thr	synonymous	Exon 30 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.3834C>T	p.Thr1278Thr	synonymous	Exon 30 of 49	ENSP00000436812.1

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1833 AN: 152210 Hom.: 41 Cov.: 33

Gnomad AFR AF: 0.0403

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00569

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00324 AC: 806 AN: 248826 AF XY: 0.00253

Gnomad AFR exome AF: 0.0416

Gnomad AMR exome AF: 0.00276

Gnomad ASJ exome AF: 0.0000998

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000408

Gnomad OTH exome AF: 0.00315

GnomAD4 exome AF: 0.00147 AC: 2155 AN: 1461232 Hom.: 42 Cov.: 33 AF XY: 0.00125 AC XY: 905 AN XY: 726910

African (AFR) AF: 0.0404 AC: 1352 AN: 33476

American (AMR) AF: 0.00333 AC: 149 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000928 AC: 8 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53314

Middle Eastern (MID) AF: 0.00659 AC: 38 AN: 5764

European-Non Finnish (NFE) AF: 0.000332 AC: 369 AN: 1111588

Other (OTH) AF: 0.00394 AC: 238 AN: 60354

GnomAD4 genome AF: 0.0120 AC: 1831 AN: 152326 Hom.: 41 Cov.: 33 AF XY: 0.0117 AC XY: 873 AN XY: 74480

African (AFR) AF: 0.0402 AC: 1670 AN: 41562

American (AMR) AF: 0.00568 AC: 87 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000691 AC: 47 AN: 68018

Other (OTH) AF: 0.0109 AC: 23 AN: 2114

Alfa AF: 0.00650 Hom.: 13

Bravo AF: 0.0141

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000415

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Interstitial lung disease 2 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.0060
DANN	Benign	0.81
PhyloP100		-2.3
Mutation Taster		=89/11	polymorphism

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: rs55913363; hg19: chr11-1261469; COSMIC: COSV71592026; COSMIC: COSV71592026;