rs188370271

chr11-1246023-C-T

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.9143C>T(p.Ala3048Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0217 in 1,589,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (0 hom., cov: 29)
  • Exomes 𝑓: 0.022 (0 hom.)
• Consequence: MUC5B NM_002458.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0550

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=0.0033162236).
• BP6: Variant 11-1246023-C-T is Benign according to our data. Variant chr11-1246023-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 403187.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0193 (2904/150498) while in subpopulation NFE AF= 0.0275 (1854/67298). AF 95% confidence interval is 0.0265. There are 0 homozygotes in gnomad4. There are 1432 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd at 2904 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3	c.9143C>T	p.Ala3048Val	missense_variant	31/49	ENST00000529681.5
MUC5B-AS1	NR_157183.1	n.57-3385G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5	c.9143C>T	p.Ala3048Val	missense_variant	31/49	5	NM_002458.3	P1
MUC5B-AS1	ENST00000532061.2	n.57-3385G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0193 AC: 2904 AN: 150380 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00539

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00540

Gnomad ASJ AF: 0.0244

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00628

Gnomad FIN AF: 0.0579

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0275

Gnomad OTH AF: 0.0155

GnomAD3 exomes AF: 0.0221 AC: 5464 AN: 247198 Hom.: 0 AF XY: 0.0218 AC XY: 2921 AN XY: 134104

Gnomad AFR exome AF: 0.00534

Gnomad AMR exome AF: 0.00418

Gnomad ASJ exome AF: 0.0219

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00748

Gnomad FIN exome AF: 0.0649

Gnomad NFE exome AF: 0.0293

Gnomad OTH exome AF: 0.0238

GnomAD4 exome AF: 0.0220 AC: 31624 AN: 1439064 Hom.: 0 Cov.: 80 AF XY: 0.0218 AC XY: 15605 AN XY: 716476

Gnomad4 AFR exome AF: 0.00307

Gnomad4 AMR exome AF: 0.00428

Gnomad4 ASJ exome AF: 0.0232

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00753

Gnomad4 FIN exome AF: 0.0647

Gnomad4 NFE exome AF: 0.0233

Gnomad4 OTH exome AF: 0.0207

GnomAD4 genome AF: 0.0193 AC: 2904 AN: 150498 Hom.: 0 Cov.: 29 AF XY: 0.0195 AC XY: 1432 AN XY: 73496

Gnomad4 AFR AF: 0.00537

Gnomad4 AMR AF: 0.00539

Gnomad4 ASJ AF: 0.0244

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00628

Gnomad4 FIN AF: 0.0579

Gnomad4 NFE AF: 0.0275

Gnomad4 OTH AF: 0.0153

Alfa AF: 0.0292 Hom.: 0

ESP6500AA AF: 0.00406 AC: 17

ESP6500EA AF: 0.0219 AC: 184

ExAC AF: 0.0267 AC: 3238

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	0.11
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.79
Cadd	Benign	1.8
Dann	Benign	0.55
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.44	T
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.033
Sift	Benign	0.15	T
Vest4		0.0080
ClinPred		0.0054	T
GERP RS		-1.3
Varity_R		0.026
gMVP		0.15

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: rs188370271; hg19: chr11-1267253;