11-1199534-C-T

Variant names:

• chr11-1199534-C-T
• rs28514396
• NM_001304359.2:c.16515+44C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001304359.2(MUC5AC):​c.16515+44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 701,422 control chromosomes in the GnomAD database, including 116,490 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 (21815 hom., cov: 34)
  • Exomes 𝑓: 0.58 (94675 hom.)
• Consequence: MUC5AC NM_001304359.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=1.958).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5AC	NM_001304359.2	c.16515+44C>T		intron_variant	Intron 46 of 48	ENST00000621226.2	NP_001291288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5AC	ENST00000621226.2	c.16515+44C>T		intron_variant	Intron 46 of 48	5	NM_001304359.2	ENSP00000485659.1

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79659 AN: 151940 Hom.: 21828 Cov.: 34

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.549

GnomAD4 exome AF: 0.583 AC: 320326 AN: 549366 Hom.: 94675 Cov.: 0 AF XY: 0.582 AC XY: 173126 AN XY: 297230

African (AFR) AF: 0.338 AC: 5343 AN: 15788

American (AMR) AF: 0.576 AC: 19983 AN: 34676

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 13670 AN: 19974

East Asian (EAS) AF: 0.649 AC: 20794 AN: 32062

South Asian (SAS) AF: 0.530 AC: 33255 AN: 62726

European-Finnish (FIN) AF: 0.555 AC: 18538 AN: 33416

Middle Eastern (MID) AF: 0.591 AC: 2397 AN: 4056

European-Non Finnish (NFE) AF: 0.597 AC: 188760 AN: 316154

Other (OTH) AF: 0.576 AC: 17586 AN: 30514

GnomAD4 genome AF: 0.524 AC: 79663 AN: 152056 Hom.: 21815 Cov.: 34 AF XY: 0.521 AC XY: 38721 AN XY: 74350

African (AFR) AF: 0.345 AC: 14314 AN: 41456

American (AMR) AF: 0.578 AC: 8840 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2403 AN: 3470

East Asian (EAS) AF: 0.671 AC: 3453 AN: 5148

South Asian (SAS) AF: 0.499 AC: 2404 AN: 4822

European-Finnish (FIN) AF: 0.544 AC: 5772 AN: 10612

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40617 AN: 67934

Other (OTH) AF: 0.546 AC: 1154 AN: 2114

Alfa AF: 0.589 Hom.: 34825

Bravo AF: 0.523

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	2.0
PhyloP100		-0.47

Splicing

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

Other links and lift over

dbSNP: rs28514396; hg19: -;