rs189329205

chr11-1246061-T-C

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.9181T>C(p.Ser3061Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0257 in 148,444 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (78 hom., cov: 29)
  • Exomes 𝑓: 0.030 (923 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC5B NM_002458.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.55

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=0.0034552217).
• BP6: Variant 11-1246061-T-C is Benign according to our data. Variant chr11-1246061-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 403189.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0257 (3816/148444) while in subpopulation NFE AF= 0.0332 (2228/67054). AF 95% confidence interval is 0.0321. There are 78 homozygotes in gnomad4. There are 1898 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 3817 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3	c.9181T>C	p.Ser3061Pro	missense_variant	31/49	ENST00000529681.5
MUC5B-AS1	NR_157183.1	n.57-3423A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5	c.9181T>C	p.Ser3061Pro	missense_variant	31/49	5	NM_002458.3	P1
MUC5B-AS1	ENST00000532061.2	n.57-3423A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0257 AC: 3817 AN: 148324 Hom.: 78 Cov.: 29

Gnomad AFR AF: 0.0138

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00767

Gnomad ASJ AF: 0.0297

Gnomad EAS AF: 0.000204

Gnomad SAS AF: 0.00842

Gnomad FIN AF: 0.0712

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0332

Gnomad OTH AF: 0.0226

GnomAD3 exomes AF: 0.0267 AC: 6661 AN: 249048 Hom.: 154 AF XY: 0.0265 AC XY: 3585 AN XY: 135136

Gnomad AFR exome AF: 0.0154

Gnomad AMR exome AF: 0.00513

Gnomad ASJ exome AF: 0.0289

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00941

Gnomad FIN exome AF: 0.0745

Gnomad NFE exome AF: 0.0345

Gnomad OTH exome AF: 0.0280

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0302 AC: 44128 AN: 1461450 Hom.: 923 Cov.: 77 AF XY: 0.0295 AC XY: 21483 AN XY: 727008

Gnomad4 AFR exome AF: 0.0121

Gnomad4 AMR exome AF: 0.00575

Gnomad4 ASJ exome AF: 0.0294

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00953

Gnomad4 FIN exome AF: 0.0729

Gnomad4 NFE exome AF: 0.0326

Gnomad4 OTH exome AF: 0.0276

GnomAD4 genome AF: 0.0257 AC: 3816 AN: 148444 Hom.: 78 Cov.: 29 AF XY: 0.0262 AC XY: 1898 AN XY: 72400

Gnomad4 AFR AF: 0.0137

Gnomad4 AMR AF: 0.00766

Gnomad4 ASJ AF: 0.0297

Gnomad4 EAS AF: 0.000204

Gnomad4 SAS AF: 0.00843

Gnomad4 FIN AF: 0.0712

Gnomad4 NFE AF: 0.0332

Gnomad4 OTH AF: 0.0224

Alfa AF: 0.0300 Hom.: 40

Bravo AF: 0.0200

ESP6500AA AF: 0.0122 AC: 51

ESP6500EA AF: 0.0239 AC: 201

ExAC AF: 0.0279 AC: 3382

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely 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	0.073
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.0070
Dann	Benign	0.41
DEOGEN2	Benign	0.035	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0027	N
LIST_S2	Benign	0.22	T
MetaRNN	Benign	0.0035	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.68	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.016
Sift	Benign	0.26	T
Vest4		0.020
ClinPred		0.0085	T
GERP RS		-6.4
Varity_R		0.061
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: rs189329205; hg19: chr11-1267291; COSMIC: COSV71590549;