11-1246095-T-C

Variant names:

• chr11-1246095-T-C
• rs55813014
• NM_002458.3:c.9215T>C

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.9215T>C​(p.Phe3072Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 1,603,330 control chromosomes in the GnomAD database, including 186,082 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 0.47 (16471 hom., cov: 28)
  • Exomes 𝑓: 0.48 (169611 hom.)
• Consequence: MUC5B NM_002458.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.13
• Publications: 25 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=7.070967E-6).
• BP6: Variant 11-1246095-T-C is Benign according to our data. Variant chr11-1246095-T-C is described in ClinVar as Benign. ClinVar VariationId is 403150.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.644 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	NM_002458.3	MANE Select	c.9215T>C	p.Phe3072Ser	missense	Exon 31 of 49	NP_002449.2
	MUC5B-AS1	NR_157183.1		n.57-3457A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.9215T>C	p.Phe3072Ser	missense	Exon 31 of 49	ENSP00000436812.1
	MUC5B-AS1	ENST00000532061.2	TSL:5	n.57-3457A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.465 AC: 68826 AN: 147874 Hom.: 16450 Cov.: 28

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.479

GnomAD2 exomes AF: 0.499 AC: 122711 AN: 245674 AF XY: 0.493

Gnomad AFR exome AF: 0.332

Gnomad AMR exome AF: 0.596

Gnomad ASJ exome AF: 0.457

Gnomad EAS exome AF: 0.660

Gnomad FIN exome AF: 0.569

Gnomad NFE exome AF: 0.475

Gnomad OTH exome AF: 0.491

GnomAD4 exome AF: 0.477 AC: 694290 AN: 1455336 Hom.: 169611 Cov.: 95 AF XY: 0.475 AC XY: 343975 AN XY: 724110

African (AFR) AF: 0.339 AC: 11219 AN: 33120

American (AMR) AF: 0.588 AC: 26290 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 11827 AN: 26080

East Asian (EAS) AF: 0.705 AC: 27970 AN: 39684

South Asian (SAS) AF: 0.436 AC: 37580 AN: 86164

European-Finnish (FIN) AF: 0.564 AC: 30059 AN: 53274

Middle Eastern (MID) AF: 0.439 AC: 2527 AN: 5752

European-Non Finnish (NFE) AF: 0.469 AC: 518474 AN: 1106450

Other (OTH) AF: 0.471 AC: 28344 AN: 60136

GnomAD4 genome AF: 0.465 AC: 68876 AN: 147994 Hom.: 16471 Cov.: 28 AF XY: 0.473 AC XY: 34168 AN XY: 72216

African (AFR) AF: 0.361 AC: 14109 AN: 39114

American (AMR) AF: 0.550 AC: 8283 AN: 15070

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1610 AN: 3436

East Asian (EAS) AF: 0.663 AC: 3309 AN: 4990

South Asian (SAS) AF: 0.448 AC: 2081 AN: 4650

European-Finnish (FIN) AF: 0.583 AC: 6060 AN: 10398

Middle Eastern (MID) AF: 0.398 AC: 113 AN: 284

European-Non Finnish (NFE) AF: 0.474 AC: 31827 AN: 67096

Other (OTH) AF: 0.484 AC: 994 AN: 2052

Alfa AF: 0.470 Hom.: 9122

Bravo AF: 0.456

ESP6500AA AF: 0.205 AC: 847

ESP6500EA AF: 0.351 AC: 2932

ExAC AF: 0.489 AC: 59177

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	0.054
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.65
DANN	Benign	0.41
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.000080	N
LIST_S2	Benign	0.44	T
MetaRNN	Benign	0.0000071	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.7	N
PhyloP100		-1.1
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.90	N
REVEL	Benign	0.037
Sift	Benign	0.40	T
Vest4		0.027
ClinPred		0.0044	T
GERP RS		-0.50
Varity_R		0.035
gMVP		0.14
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: rs55813014; hg19: chr11-1267325; COSMIC: COSV71589890;