rs139052978

Variant names:

• chr11-1245928-G-A
• rs139052978
• NM_002458.3:c.9048G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-1245928-G-A
• chr11-1245928-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002458.3(MUC5B):​c.9048G>A​(p.Pro3016Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 1,608,322 control chromosomes in the GnomAD database, including 599 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (38 hom., cov: 29)
  • Exomes 𝑓: 0.023 (561 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.67
• Publications: 2 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 11-1245928-G-A is Benign according to our data. Variant chr11-1245928-G-A is described in ClinVar as Benign. ClinVar VariationId is 403149.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.66 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0179 (2633/147404) while in subpopulation NFE AF = 0.0268 (1782/66530). AF 95% confidence interval is 0.0257. There are 38 homozygotes in GnomAd4. There are 1286 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 38 AR gene

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.9048G>A	p.Pro3016Pro	synonymous	Exon 31 of 49	NP_002449.2
	MUC5B-AS1	NR_157183.1		n.57-3290C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5B	ENST00000529681.5	TSL:5 MANE Select	c.9048G>A	p.Pro3016Pro	synonymous	Exon 31 of 49	ENSP00000436812.1
	MUC5B-AS1	ENST00000532061.2	TSL:5	n.57-3290C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0179 AC: 2633 AN: 147280 Hom.: 38 Cov.: 29

Gnomad AFR AF: 0.00423

Gnomad AMI AF: 0.00336

Gnomad AMR AF: 0.0144

Gnomad ASJ AF: 0.00857

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00886

Gnomad FIN AF: 0.0355

Gnomad MID AF: 0.0219

Gnomad NFE AF: 0.0268

Gnomad OTH AF: 0.0155

GnomAD2 exomes AF: 0.0176 AC: 4393 AN: 248956 AF XY: 0.0180

Gnomad AFR exome AF: 0.00342

Gnomad AMR exome AF: 0.00762

Gnomad ASJ exome AF: 0.0110

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.0330

Gnomad NFE exome AF: 0.0258

Gnomad OTH exome AF: 0.0180

GnomAD4 exome AF: 0.0235 AC: 34275 AN: 1460918 Hom.: 561 Cov.: 70 AF XY: 0.0230 AC XY: 16696 AN XY: 726756

African (AFR) AF: 0.00413 AC: 138 AN: 33454

American (AMR) AF: 0.00821 AC: 367 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.0114 AC: 298 AN: 26110

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39678

South Asian (SAS) AF: 0.00754 AC: 650 AN: 86228

European-Finnish (FIN) AF: 0.0308 AC: 1639 AN: 53272

Middle Eastern (MID) AF: 0.0219 AC: 126 AN: 5766

European-Non Finnish (NFE) AF: 0.0268 AC: 29741 AN: 1111374

Other (OTH) AF: 0.0218 AC: 1314 AN: 60342

GnomAD4 genome AF: 0.0179 AC: 2633 AN: 147404 Hom.: 38 Cov.: 29 AF XY: 0.0179 AC XY: 1286 AN XY: 71798

African (AFR) AF: 0.00421 AC: 168 AN: 39864

American (AMR) AF: 0.0144 AC: 213 AN: 14824

Ashkenazi Jewish (ASJ) AF: 0.00857 AC: 29 AN: 3382

East Asian (EAS) AF: 0.00 AC: 0 AN: 4860

South Asian (SAS) AF: 0.00887 AC: 41 AN: 4622

European-Finnish (FIN) AF: 0.0355 AC: 360 AN: 10154

Middle Eastern (MID) AF: 0.0231 AC: 6 AN: 260

European-Non Finnish (NFE) AF: 0.0268 AC: 1782 AN: 66530

Other (OTH) AF: 0.0154 AC: 31 AN: 2014

Alfa AF: 0.0168 Hom.: 10

Bravo AF: 0.0151

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.0243

EpiControl AF: 0.0250

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.9
DANN	Benign	0.56
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs139052978; hg19: chr11-1267158; COSMIC: COSV71591237;