rs60268710

Variant names:

• chr11-1246332-C-T
• rs60268710
• NM_002458.3:c.9452C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000529681.5(MUC5B):​c.9452C>T​(p.Thr3151Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,612,516 control chromosomes in the GnomAD database, including 81,152 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6846 hom., cov: 31)
  • Exomes 𝑓: 0.31 (74306 hom.)
• Consequence: MUC5B ENST00000529681.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.10
• Publications: 20 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-AS1 (HGNC:53936): (MUC5B antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.736798E-5).
• BP6: Variant 11-1246332-C-T is Benign according to our data. Variant chr11-1246332-C-T is described in ClinVar as Benign. ClinVar VariationId is 403151.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000529681.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	NM_002458.3	MANE Select	c.9452C>T	p.Thr3151Met	missense	Exon 31 of 49	NP_002449.2
	MUC5B-AS1	NR_157183.1		n.56+3289G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.9452C>T	p.Thr3151Met	missense	Exon 31 of 49	ENSP00000436812.1
	MUC5B-AS1	ENST00000532061.2	TSL:5	n.56+3289G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44102 AN: 151132 Hom.: 6832 Cov.: 31

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.313

GnomAD2 exomes AF: 0.322 AC: 80076 AN: 248712 AF XY: 0.320

Gnomad AFR exome AF: 0.207

Gnomad AMR exome AF: 0.308

Gnomad ASJ exome AF: 0.298

Gnomad EAS exome AF: 0.609

Gnomad FIN exome AF: 0.287

Gnomad NFE exome AF: 0.316

Gnomad OTH exome AF: 0.313

GnomAD4 exome AF: 0.313 AC: 457578 AN: 1461266 Hom.: 74306 Cov.: 122 AF XY: 0.312 AC XY: 226464 AN XY: 726920

African (AFR) AF: 0.210 AC: 7026 AN: 33442

American (AMR) AF: 0.307 AC: 13744 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 7645 AN: 26126

East Asian (EAS) AF: 0.601 AC: 23861 AN: 39698

South Asian (SAS) AF: 0.282 AC: 24307 AN: 86242

European-Finnish (FIN) AF: 0.287 AC: 15254 AN: 53222

Middle Eastern (MID) AF: 0.289 AC: 1664 AN: 5764

European-Non Finnish (NFE) AF: 0.310 AC: 345078 AN: 1111710

Other (OTH) AF: 0.315 AC: 18999 AN: 60348

GnomAD4 genome AF: 0.292 AC: 44136 AN: 151250 Hom.: 6846 Cov.: 31 AF XY: 0.293 AC XY: 21643 AN XY: 73870

African (AFR) AF: 0.214 AC: 8825 AN: 41180

American (AMR) AF: 0.331 AC: 5055 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1030 AN: 3458

East Asian (EAS) AF: 0.592 AC: 2953 AN: 4986

South Asian (SAS) AF: 0.289 AC: 1382 AN: 4786

European-Finnish (FIN) AF: 0.282 AC: 2976 AN: 10558

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.308 AC: 20844 AN: 67722

Other (OTH) AF: 0.320 AC: 672 AN: 2102

Alfa AF: 0.299 Hom.: 2231

Bravo AF: 0.294

ESP6500AA AF: 0.192 AC: 782

ESP6500EA AF: 0.298 AC: 2471

ExAC AF: 0.320 AC: 38643

EpiCase AF: 0.310

EpiControl AF: 0.313

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.9
DANN	Benign	0.71
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0090	N
LIST_S2	Benign	0.68	T
MetaRNN	Benign	0.000037	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-2.1
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.044
Sift	Uncertain	0.026	D
Vest4		0.032
ClinPred		0.0053	T
GERP RS		-3.5
Varity_R		0.019
gMVP		0.27
Mutation Taster		=100/0	polymorphism (auto)

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: rs60268710; hg19: chr11-1267562; COSMIC: COSV101499941;