dbSNP rs55846509: MUC5AC:p.Arg47Gln (chr11-1160678-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001304359.2(MUC5AC):c.140G>A(p.Arg47Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0203 in 1,609,140 control chromosomes in the GnomAD database, including 424 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.015 ( 33 hom., cov: 33)

Exomes 𝑓: 0.021 ( 391 hom. )

Consequence

MUC5AC
NM_001304359.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.38

Variant links:

Genes affected

MUC5AC (HGNC:7515): (mucin 5AC, oligomeric mucus/gel-forming) Predicted to be an extracellular matrix structural constituent. Involved in phosphatidylinositol-mediated signaling. Located in cytoplasm; extracellular space; and mucus layer. Implicated in dry eye syndrome. Biomarker of several diseases, including Sjogren's syndrome; biliary tract disease (multiple); cystic fibrosis; eye disease (multiple); and pancreatic cancer (multiple). [provided by Alliance of Genome Resources, Apr 2022]

MUC5AC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031018555).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0155 (2358/152290) while in subpopulation NFE AF= 0.0237 (1611/68004). AF 95% confidence interval is 0.0227. There are 33 homozygotes in gnomad4. There are 1134 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5AC	NM_001304359.2 link	c.140G>A	p.Arg47Gln	missense_variant	Exon 2 of 49	ENST00000621226.2	NP_001291288.1	P98088

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5AC	ENST00000621226.2 link	c.140G>A	p.Arg47Gln	missense_variant	Exon 2 of 49	5	NM_001304359.2	ENSP00000485659.1		P98088

Frequencies

GnomAD3 genomes

AF:

0.0155

AC:

2358

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00393

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0116

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00496

Gnomad FIN

AF:

0.0315

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0237

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.0156

AC:

3678

AN:

235612

Hom.:

AF XY:

0.0157

AC XY:

2038

AN XY:

130026

show subpopulations

Gnomad AFR exome

AF:

0.00305

Gnomad AMR exome

AF:

0.00933

Gnomad ASJ exome

AF:

0.00657

Gnomad EAS exome

AF:

0.0000566

Gnomad SAS exome

AF:

0.00560

Gnomad FIN exome

AF:

0.0311

Gnomad NFE exome

AF:

0.0226

Gnomad OTH exome

AF:

0.0164

GnomAD4 exome

AF:

0.0208

AC:

30295

AN:

1456850

Hom.:

391

Cov.:

AF XY:

0.0202

AC XY:

14621

AN XY:

724706

show subpopulations

Gnomad4 AFR exome

AF:

0.00338

Gnomad4 AMR exome

AF:

0.00981

Gnomad4 ASJ exome

AF:

0.00656

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00584

Gnomad4 FIN exome

AF:

0.0277

Gnomad4 NFE exome

AF:

0.0238

Gnomad4 OTH exome

AF:

0.0191

GnomAD4 genome

AF:

0.0155

AC:

2358

AN:

152290

Hom.:

Cov.:

AF XY:

0.0152

AC XY:

1134

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00392

Gnomad4 AMR

AF:

0.0116

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00497

Gnomad4 FIN

AF:

0.0315

Gnomad4 NFE

AF:

0.0237

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.0186

Hom.:

Bravo

AF:

0.0140

ESP6500AA

AF:

0.00400

AC:

ESP6500EA

AF:

0.0254

AC:

101

ExAC

AF:

0.0164

AC:

1906

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.46

DANN

Benign

0.66

DEOGEN2

Benign

0.026

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0018

MetaRNN

Benign

0.0031

MetaSVM

Benign

-0.96

Sift4G

Benign

0.42

Vest4

0.026

ClinPred

0.00028

GERP RS

-1.7

Varity_R

0.028

gMVP

0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over