chr11-1167980-C-T

Position:

• chr11-1167980-C-T

Variant summary

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

The NM_001304359.2(MUC5AC):​c.1490C>T​(p.Ala497Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0405 in 1,550,168 control chromosomes in the GnomAD database, including 1,506 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 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 0.033 (109 hom., cov: 34)
  • Exomes 𝑓: 0.041 (1397 hom.)
• Consequence: MUC5AC NM_001304359.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50

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=0.004837781).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5AC	NM_001304359.2	c.1490C>T	p.Ala497Val	missense_variant	12/49	ENST00000621226.2	NP_001291288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5AC	ENST00000621226.2	c.1490C>T	p.Ala497Val	missense_variant	12/49	5	NM_001304359.2	ENSP00000485659.1

Frequencies

GnomAD3 genomes AF: 0.0331 AC: 5030 AN: 152148 Hom.: 109 Cov.: 34

Gnomad AFR AF: 0.00697

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.0350

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0493

Gnomad FIN AF: 0.0418

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.0427

Gnomad OTH AF: 0.0402

GnomAD4 exome AF: 0.0414 AC: 57824 AN: 1397902 Hom.: 1397 Cov.: 34 AF XY: 0.0420 AC XY: 28974 AN XY: 689472

Gnomad4 AFR exome AF: 0.00554

Gnomad4 AMR exome AF: 0.0307

Gnomad4 ASJ exome AF: 0.102

Gnomad4 EAS exome AF: 0.000168

Gnomad4 SAS exome AF: 0.0559

Gnomad4 FIN exome AF: 0.0421

Gnomad4 NFE exome AF: 0.0411

Gnomad4 OTH exome AF: 0.0470

GnomAD4 genome AF: 0.0330 AC: 5026 AN: 152266 Hom.: 109 Cov.: 34 AF XY: 0.0329 AC XY: 2446 AN XY: 74452

Gnomad4 AFR AF: 0.00695

Gnomad4 AMR AF: 0.0350

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0498

Gnomad4 FIN AF: 0.0418

Gnomad4 NFE AF: 0.0426

Gnomad4 OTH AF: 0.0384

Alfa AF: 0.0411 Hom.: 43

Bravo AF: 0.0325

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_noAF	Benign	-0.95
CADD	Benign	22
DEOGEN2	Benign	0.22	T
MetaRNN	Benign	0.0048	T
Sift4G	Uncertain	0.027	D
Vest4		0.064
gMVP		0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28403537; hg19: chr11-1161315;