rs960833835

Variant names:

• chr11-1174770-C-T
• rs960833835
• NM_001304359.2:c.2093-112C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001304359.2(MUC5AC):​c.2093-112C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 310,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: MUC5AC NM_001304359.2 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.79
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (Cadd=1.888).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304359.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5AC	NM_001304359.2	MANE Select	c.2093-112C>T		intron	N/A	NP_001291288.1	P98088

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5AC	ENST00000621226.2	TSL:5 MANE Select	c.2093-112C>T		intron	N/A	ENSP00000485659.1	P98088

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.0000129 AC: 4 AN: 310632 Hom.: 0 Cov.: 3 AF XY: 0.0000185 AC XY: 3 AN XY: 162012

African (AFR) AF: 0.00 AC: 0 AN: 8016

American (AMR) AF: 0.00 AC: 0 AN: 9054

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10572

East Asian (EAS) AF: 0.00 AC: 0 AN: 23546

South Asian (SAS) AF: 0.00 AC: 0 AN: 20458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24892

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1520

European-Non Finnish (NFE) AF: 0.0000207 AC: 4 AN: 193260

Other (OTH) AF: 0.00 AC: 0 AN: 19314

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Lung adenocarcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Benign	1.9
PhyloP100		-1.8

Splicing

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

Other links and lift over

dbSNP: rs960833835;