11-1242293-G-A

Position:

• chr11-1242293-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002458.3(MUC5B):​c.5413G>A​(p.Gly1805Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0752 in 1,613,860 control chromosomes in the GnomAD database, including 5,101 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.067 (428 hom., cov: 32)
  • Exomes 𝑓: 0.076 (4673 hom.)
• Consequence: MUC5B NM_002458.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.378

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024515688).
• BP6: Variant 11-1242293-G-A is Benign according to our data. Variant chr11-1242293-G-A is described in ClinVar as [Benign]. Clinvar id is 1249409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.089 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3	c.5413G>A	p.Gly1805Ser	missense_variant	31/49	ENST00000529681.5
MUC5B-AS1	NR_157183.1	n.402C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5	c.5413G>A	p.Gly1805Ser	missense_variant	31/49	5	NM_002458.3	P1
MUC5B-AS1	ENST00000532061.2	n.402C>T		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes AF: 0.0669 AC: 10171 AN: 152118 Hom.: 428 Cov.: 32

Gnomad AFR AF: 0.0225

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.0932

Gnomad ASJ AF: 0.0997

Gnomad EAS AF: 0.0572

Gnomad SAS AF: 0.0916

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0743

Gnomad OTH AF: 0.0712

GnomAD3 exomes AF: 0.0845 AC: 21067 AN: 249244 Hom.: 1075 AF XY: 0.0848 AC XY: 11464 AN XY: 135228

Gnomad AFR exome AF: 0.0211

Gnomad AMR exome AF: 0.130

Gnomad ASJ exome AF: 0.0885

Gnomad EAS exome AF: 0.0496

Gnomad SAS exome AF: 0.0917

Gnomad FIN exome AF: 0.125

Gnomad NFE exome AF: 0.0747

Gnomad OTH exome AF: 0.0847

GnomAD4 exome AF: 0.0761 AC: 111197 AN: 1461624 Hom.: 4673 Cov.: 66 AF XY: 0.0771 AC XY: 56059 AN XY: 727098

Gnomad4 AFR exome AF: 0.0208

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.0920

Gnomad4 EAS exome AF: 0.102

Gnomad4 SAS exome AF: 0.0930

Gnomad4 FIN exome AF: 0.126

Gnomad4 NFE exome AF: 0.0707

Gnomad4 OTH exome AF: 0.0729

GnomAD4 genome AF: 0.0668 AC: 10165 AN: 152236 Hom.: 428 Cov.: 32 AF XY: 0.0707 AC XY: 5259 AN XY: 74426

Gnomad4 AFR AF: 0.0225

Gnomad4 AMR AF: 0.0930

Gnomad4 ASJ AF: 0.0997

Gnomad4 EAS AF: 0.0574

Gnomad4 SAS AF: 0.0919

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.0743

Gnomad4 OTH AF: 0.0700

Alfa AF: 0.0767 Hom.: 970

Bravo AF: 0.0625

TwinsUK AF: 0.0739 AC: 274

ALSPAC AF: 0.0732 AC: 282

ESP6500AA AF: 0.0170 AC: 68

ESP6500EA AF: 0.0716 AC: 596

ExAC AF: 0.0800 AC: 9674

Asia WGS AF: 0.0580 AC: 203 AN: 3478

EpiCase AF: 0.0786

EpiControl AF: 0.0770

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Benign	0.85
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.055
Sift	Benign	0.18	T
Vest4		0.046
ClinPred		0.032	T
GERP RS		1.1
Varity_R		0.13
gMVP		0.87

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: rs1541314; hg19: chr11-1263523; COSMIC: COSV71590098; COSMIC: COSV71590098;