rs55856616

chr11-1259008-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002458.3(MUC5B):c.16660G>A(p.Asp5554Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0371 in 1,560,460 control chromosomes in the GnomAD database, including 1,401 homozygotes. 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.049 (237 hom., cov: 32)
  • Exomes 𝑓: 0.036 (1164 hom.)
• Consequence: MUC5B NM_002458.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.46

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0021681786).
• BP6: Variant 11-1259008-G-A is Benign according to our data. Variant chr11-1259008-G-A is described in ClinVar as [Benign]. Clinvar id is 164011.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3	c.16660G>A	p.Asp5554Asn	missense_variant	44/49	ENST00000529681.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5	c.16660G>A	p.Asp5554Asn	missense_variant	44/49	5	NM_002458.3	P1
MUC5B	ENST00000526859.1	c.295G>A	p.Asp99Asn	missense_variant	4/6	3

Frequencies

GnomAD3 genomes AF: 0.0485 AC: 7372 AN: 152012 Hom.: 234 Cov.: 32

Gnomad AFR AF: 0.0935

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.0327

Gnomad ASJ AF: 0.0764

Gnomad EAS AF: 0.00309

Gnomad SAS AF: 0.0658

Gnomad FIN AF: 0.00839

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0321

Gnomad OTH AF: 0.0464

GnomAD3 exomes AF: 0.0375 AC: 6415 AN: 171098 Hom.: 188 AF XY: 0.0396 AC XY: 3606 AN XY: 91012

Gnomad AFR exome AF: 0.0988

Gnomad AMR exome AF: 0.0227

Gnomad ASJ exome AF: 0.0877

Gnomad EAS exome AF: 0.00324

Gnomad SAS exome AF: 0.0701

Gnomad FIN exome AF: 0.00928

Gnomad NFE exome AF: 0.0307

Gnomad OTH exome AF: 0.0428

GnomAD4 exome AF: 0.0359 AC: 50572 AN: 1408330 Hom.: 1164 Cov.: 32 AF XY: 0.0371 AC XY: 25795 AN XY: 695514

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.0250

Gnomad4 ASJ exome AF: 0.0834

Gnomad4 EAS exome AF: 0.00212

Gnomad4 SAS exome AF: 0.0705

Gnomad4 FIN exome AF: 0.0101

Gnomad4 NFE exome AF: 0.0324

Gnomad4 OTH exome AF: 0.0421

GnomAD4 genome AF: 0.0486 AC: 7390 AN: 152130 Hom.: 237 Cov.: 32 AF XY: 0.0472 AC XY: 3510 AN XY: 74396

Gnomad4 AFR AF: 0.0939

Gnomad4 AMR AF: 0.0327

Gnomad4 ASJ AF: 0.0764

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0650

Gnomad4 FIN AF: 0.00839

Gnomad4 NFE AF: 0.0321

Gnomad4 OTH AF: 0.0449

Alfa AF: 0.0375 Hom.: 155

Bravo AF: 0.0520

TwinsUK AF: 0.0289 AC: 107

ALSPAC AF: 0.0327 AC: 126

ESP6500AA AF: 0.0845 AC: 329

ESP6500EA AF: 0.0301 AC: 247

ExAC AF: 0.0239 AC: 2681

Asia WGS AF: 0.0390 AC: 136 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

Asp5554Asn in exon 44 of MUC5B: This variant is not expected to have clinical si gnificance because it has been identified in 8.4% (329/3894) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs55856616). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.85
Cadd	Benign	6.3
Dann	Benign	0.76
DEOGEN2	Benign	0.016	T;T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.56	T;T
MetaRNN	Benign	0.0022	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.71	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.019
Sift	Benign	0.30	T;T
Vest4		0.015
ClinPred		0.0027	T
GERP RS		1.6
Varity_R		0.041
gMVP		0.89

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: rs55856616; hg19: chr11-1280238;