rs55846509

Positions:

• chr11-1160678-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38

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]

ACMG classification

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/exons	MANE	Protein	UniProt
MUC5AC	NM_001304359.2	c.140G>A	p.Arg47Gln	missense_variant	2/49	ENST00000621226.2	NP_001291288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5AC	ENST00000621226.2	c.140G>A	p.Arg47Gln	missense_variant	2/49	5	NM_001304359.2	ENSP00000485659.1

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2358 AN: 152172 Hom.: 33 Cov.: 33

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.: 55 AF XY: 0.0157 AC XY: 2038 AN XY: 130026

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.: 32 AF XY: 0.0202 AC XY: 14621 AN XY: 724706

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.: 33 Cov.: 33 AF XY: 0.0152 AC XY: 1134 AN XY: 74474

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.: 19

Bravo AF: 0.0140

ESP6500AA AF: 0.00400 AC: 7

ESP6500EA AF: 0.0254 AC: 101

ExAC AF: 0.0164 AC: 1906

Asia WGS AF: 0.00260 AC: 9 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	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.46
DANN	Benign	0.66
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0018	N
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-0.96	T
Sift4G	Benign	0.42	T
Vest4		0.026
ClinPred		0.00028	T
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

Other links and lift over

dbSNP: rs55846509; hg19: chr11-1154294; COSMIC: COSV99050037;