11-1244757-C-T

Variant names:

• chr11-1244757-C-T
• rs3021158
• NM_002458.3:c.7877C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002458.3(MUC5B):​c.7877C>T​(p.Thr2626Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00864 in 149,014 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T2626R) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0086 (7 hom., cov: 30)
  • Exomes 𝑓: 0.0013 (5 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC5B NM_002458.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390

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-AS1 (HGNC:53936): (MUC5B antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005446613).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00864 (1287/149014) while in subpopulation AFR AF= 0.0163 (671/41228). AF 95% confidence interval is 0.0153. There are 7 homozygotes in gnomad4. There are 625 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1287 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.7877C>T	p.Thr2626Met	missense_variant	Exon 31 of 49	ENST00000529681.5	NP_002449.2
MUC5B-AS1	NR_157183.1	n.57-2119G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.7877C>T	p.Thr2626Met	missense_variant	Exon 31 of 49	5	NM_002458.3	ENSP00000436812.1
MUC5B-AS1	ENST00000532061.2	n.57-2119G>A		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.00864 AC: 1286 AN: 148894 Hom.: 7 Cov.: 30

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00198

Gnomad ASJ AF: 0.00445

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00272

Gnomad FIN AF: 0.0129

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00626

Gnomad OTH AF: 0.00732

GnomAD3 exomes AF: 0.00233 AC: 559 AN: 239454 Hom.: 3 AF XY: 0.00199 AC XY: 258 AN XY: 129888

Gnomad AFR exome AF: 0.0166

Gnomad AMR exome AF: 0.000496

Gnomad ASJ exome AF: 0.00156

Gnomad EAS exome AF: 0.000334

Gnomad SAS exome AF: 0.000398

Gnomad FIN exome AF: 0.00336

Gnomad NFE exome AF: 0.00169

Gnomad OTH exome AF: 0.00155

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00128 AC: 1778 AN: 1393864 Hom.: 5 Cov.: 141 AF XY: 0.00120 AC XY: 831 AN XY: 694168

Gnomad4 AFR exome AF: 0.0167

Gnomad4 AMR exome AF: 0.000653

Gnomad4 ASJ exome AF: 0.000523

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.000247

Gnomad4 FIN exome AF: 0.00289

Gnomad4 NFE exome AF: 0.000875

Gnomad4 OTH exome AF: 0.00142

GnomAD4 genome AF: 0.00864 AC: 1287 AN: 149014 Hom.: 7 Cov.: 30 AF XY: 0.00858 AC XY: 625 AN XY: 72850

Gnomad4 AFR AF: 0.0163

Gnomad4 AMR AF: 0.00198

Gnomad4 ASJ AF: 0.00445

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00293

Gnomad4 FIN AF: 0.0129

Gnomad4 NFE AF: 0.00626

Gnomad4 OTH AF: 0.00725

Alfa AF: 0.0161 Hom.: 160

ExAC AF: 0.0130 AC: 1571

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	16
DANN	Benign	0.61
DEOGEN2	Benign	0.048	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.0054	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.055
Sift	Pathogenic	0.0	D
Vest4		0.071
ClinPred		0.014	T
GERP RS		0.12
Varity_R		0.046
gMVP		0.29

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: rs3021158; hg19: chr11-1265987;