11-1199236-G-T

Position:

• chr11-1199236-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001304359.2(MUC5AC):​c.16395+51G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 724,058 control chromosomes in the GnomAD database, including 10,479 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 0.16 (2249 hom., cov: 32)
  • Exomes 𝑓: 0.15 (8230 hom.)
• Consequence: MUC5AC NM_001304359.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329

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 (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5AC	NM_001304359.2	c.16395+51G>T		intron_variant		ENST00000621226.2	NP_001291288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5AC	ENST00000621226.2	c.16395+51G>T		intron_variant		5	NM_001304359.2	ENSP00000485659.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24575 AN: 151986 Hom.: 2249 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.0598

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.140

GnomAD4 exome AF: 0.155 AC: 88601 AN: 571954 Hom.: 8230 Cov.: 0 AF XY: 0.150 AC XY: 46572 AN XY: 310678

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.0898

Gnomad4 ASJ exome AF: 0.0734

Gnomad4 EAS exome AF: 0.00372

Gnomad4 SAS exome AF: 0.0641

Gnomad4 FIN exome AF: 0.246

Gnomad4 NFE exome AF: 0.193

Gnomad4 OTH exome AF: 0.153

GnomAD4 genome AF: 0.162 AC: 24571 AN: 152104 Hom.: 2249 Cov.: 32 AF XY: 0.161 AC XY: 11988 AN XY: 74352

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.0726

Gnomad4 EAS AF: 0.00425

Gnomad4 SAS AF: 0.0601

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.139

Alfa AF: 0.178 Hom.: 295

Bravo AF: 0.151

Asia WGS AF: 0.0410 AC: 143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.2
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35288961; hg19: chr11-1220462;