rs117736426

Positions:

• chr11-1244709-C-G
• chr11-1244709-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002458.3(MUC5B):​c.7829C>G​(p.Thr2610Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0281 in 1,610,006 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (0 hom., cov: 31)
  • Exomes 𝑓: 0.029 (1 hom.)
• Consequence: MUC5B NM_002458.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.172

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00386253).
• BP6: Variant 11-1244709-C-G is Benign according to our data. Variant chr11-1244709-C-G is described in ClinVar as [Benign]. Clinvar id is 403144.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0188 (2830/150888) while in subpopulation NFE AF= 0.0244 (1644/67278). AF 95% confidence interval is 0.0235. There are 0 homozygotes in gnomad4. There are 1422 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2830 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3	c.7829C>G	p.Thr2610Ser	missense_variant	31/49	ENST00000529681.5
MUC5B-AS1	NR_157183.1	n.57-2071G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5	c.7829C>G	p.Thr2610Ser	missense_variant	31/49	5	NM_002458.3	P1
MUC5B-AS1	ENST00000532061.2	n.57-2071G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0188 AC: 2831 AN: 150770 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00539

Gnomad ASJ AF: 0.0215

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00562

Gnomad FIN AF: 0.0492

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0244

Gnomad OTH AF: 0.0160

GnomAD3 exomes AF: 0.0229 AC: 5665 AN: 247676 Hom.: 0 AF XY: 0.0228 AC XY: 3071 AN XY: 134466

Gnomad AFR exome AF: 0.0133

Gnomad AMR exome AF: 0.00349

Gnomad ASJ exome AF: 0.0244

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00747

Gnomad FIN exome AF: 0.0697

Gnomad NFE exome AF: 0.0290

Gnomad OTH exome AF: 0.0211

GnomAD4 exome AF: 0.0290 AC: 42363 AN: 1459118 Hom.: 1 Cov.: 151 AF XY: 0.0284 AC XY: 20612 AN XY: 725838

Gnomad4 AFR exome AF: 0.0116

Gnomad4 AMR exome AF: 0.00553

Gnomad4 ASJ exome AF: 0.0280

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00882

Gnomad4 FIN exome AF: 0.0673

Gnomad4 NFE exome AF: 0.0316

Gnomad4 OTH exome AF: 0.0263

GnomAD4 genome AF: 0.0188 AC: 2830 AN: 150888 Hom.: 0 Cov.: 31 AF XY: 0.0193 AC XY: 1422 AN XY: 73782

Gnomad4 AFR AF: 0.0112

Gnomad4 AMR AF: 0.00538

Gnomad4 ASJ AF: 0.0215

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00542

Gnomad4 FIN AF: 0.0492

Gnomad4 NFE AF: 0.0244

Gnomad4 OTH AF: 0.0158

Alfa AF: 0.0151 Hom.: 0

ESP6500AA AF: 0.0160 AC: 67

ESP6500EA AF: 0.0325 AC: 273

ExAC AF: 0.0273 AC: 3302

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.0
DANN	Benign	0.63
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.15	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.014
Sift	Pathogenic	0.0	D
Vest4		0.050
ClinPred		0.011	T
GERP RS		0.40
Varity_R		0.10
gMVP		0.14

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: rs117736426; hg19: chr11-1265939;