11-1245369-C-T

Variant names:

• chr11-1245369-C-T
• rs139960671
• NM_002458.3:c.8489C>T

Variant summary

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

The NM_002458.3(MUC5B):​c.8489C>T​(p.Pro2830Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,568,878 control chromosomes in the GnomAD database, including 54,294 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (3022 hom., cov: 21)
  • Exomes 𝑓: 0.19 (51272 hom.)
• Consequence: MUC5B NM_002458.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.74
• Publications: 7 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=0.0060741007).
• BP6: Variant 11-1245369-C-T is Benign according to our data. Variant chr11-1245369-C-T is described in ClinVar as Benign. ClinVar VariationId is 403146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

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.8489C>T	p.Pro2830Leu	missense	Exon 31 of 49	NP_002449.2	Q9HC84
	MUC5B-AS1	NR_157183.1		n.57-2731G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.8489C>T	p.Pro2830Leu	missense	Exon 31 of 49	ENSP00000436812.1	Q9HC84
	MUC5B-AS1	ENST00000532061.2	TSL:5	n.57-2731G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.139 AC: 19212 AN: 137856 Hom.: 3019 Cov.: 21

Gnomad AFR AF: 0.0353

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.00502

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.132

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.137

GnomAD2 exomes AF: 0.166 AC: 39772 AN: 239792 AF XY: 0.173

Gnomad AFR exome AF: 0.0328

Gnomad AMR exome AF: 0.101

Gnomad ASJ exome AF: 0.177

Gnomad EAS exome AF: 0.00329

Gnomad FIN exome AF: 0.273

Gnomad NFE exome AF: 0.207

Gnomad OTH exome AF: 0.176

GnomAD4 exome AF: 0.191 AC: 272927 AN: 1430906 Hom.: 51272 Cov.: 106 AF XY: 0.191 AC XY: 135906 AN XY: 712088

African (AFR) AF: 0.0300 AC: 992 AN: 33042

American (AMR) AF: 0.100 AC: 4173 AN: 41690

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 4305 AN: 25648

East Asian (EAS) AF: 0.00198 AC: 78 AN: 39378

South Asian (SAS) AF: 0.165 AC: 13900 AN: 84258

European-Finnish (FIN) AF: 0.233 AC: 11799 AN: 50634

Middle Eastern (MID) AF: 0.171 AC: 695 AN: 4058

European-Non Finnish (NFE) AF: 0.207 AC: 226416 AN: 1093022

Other (OTH) AF: 0.179 AC: 10569 AN: 59176

GnomAD4 genome AF: 0.139 AC: 19216 AN: 137972 Hom.: 3022 Cov.: 21 AF XY: 0.141 AC XY: 9392 AN XY: 66548

African (AFR) AF: 0.0351 AC: 1340 AN: 38168

American (AMR) AF: 0.127 AC: 1683 AN: 13288

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 518 AN: 3246

East Asian (EAS) AF: 0.00503 AC: 25 AN: 4968

South Asian (SAS) AF: 0.152 AC: 615 AN: 4044

European-Finnish (FIN) AF: 0.255 AC: 2152 AN: 8450

Middle Eastern (MID) AF: 0.143 AC: 40 AN: 280

European-Non Finnish (NFE) AF: 0.198 AC: 12410 AN: 62798

Other (OTH) AF: 0.139 AC: 265 AN: 1910

Alfa AF: 0.163 Hom.: 762

ESP6500AA AF: 0.0401 AC: 162

ESP6500EA AF: 0.209 AC: 1706

ExAC AF: 0.166 AC: 19621

Asia WGS AF: 0.0740 AC: 256 AN: 3456

ClinVar

ClinVar submissions

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	0.080
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.069
DANN	Benign	0.85
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.40	T
MetaRNN	Benign	0.0061	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		-3.7
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.0080
Sift	Benign	0.058	T
Vest4		0.011
ClinPred		0.00065	T
GERP RS		-0.90
Varity_R		0.028
gMVP		0.42
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: rs139960671; hg19: chr11-1266599; COSMIC: COSV71589889;