rs1132440

Positions:

• chr11-1200591-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001304359.2(MUC5AC):​c.16854G>C​(p.Arg5618Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 764,098 control chromosomes in the GnomAD database, including 126,999 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.52 (21612 hom., cov: 34)
  • Exomes 𝑓: 0.58 (105387 hom.)
• Consequence: MUC5AC NM_001304359.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.666

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-0.666 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5AC	NM_001304359.2	c.16854G>C	p.Arg5618Arg	synonymous_variant	49/49	ENST00000621226.2	NP_001291288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5AC	ENST00000621226.2	c.16854G>C	p.Arg5618Arg	synonymous_variant	49/49	5	NM_001304359.2	ENSP00000485659.1

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79168 AN: 151950 Hom.: 21624 Cov.: 34

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.543

GnomAD3 exomes AF: 0.578 AC: 130669 AN: 226102 Hom.: 38617 AF XY: 0.581 AC XY: 73015 AN XY: 125668

Gnomad AFR exome AF: 0.333

Gnomad AMR exome AF: 0.576

Gnomad ASJ exome AF: 0.685

Gnomad EAS exome AF: 0.692

Gnomad SAS exome AF: 0.520

Gnomad FIN exome AF: 0.551

Gnomad NFE exome AF: 0.601

Gnomad OTH exome AF: 0.588

GnomAD4 exome AF: 0.582 AC: 356436 AN: 612030 Hom.: 105387 Cov.: 0 AF XY: 0.582 AC XY: 194631 AN XY: 334536

Gnomad4 AFR exome AF: 0.328

Gnomad4 AMR exome AF: 0.576

Gnomad4 ASJ exome AF: 0.684

Gnomad4 EAS exome AF: 0.654

Gnomad4 SAS exome AF: 0.527

Gnomad4 FIN exome AF: 0.555

Gnomad4 NFE exome AF: 0.597

Gnomad4 OTH exome AF: 0.573

GnomAD4 genome AF: 0.521 AC: 79173 AN: 152068 Hom.: 21612 Cov.: 34 AF XY: 0.517 AC XY: 38448 AN XY: 74336

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.692

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.499

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.540

Alfa AF: 0.570 Hom.: 4651

Bravo AF: 0.520

Asia WGS AF: 0.482 AC: 1678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.38
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1132440; hg19: chr11-1221817; COSMIC: COSV64369389;