NM_001080543.2:c.-162A>C

Variant names:

• chr19-3626924-T-G
• rs2271875
• NM_001080543.2:c.-162A>C

Variant summary

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

The NM_001080543.2(CACTIN):​c.-162A>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000219 in 456,800 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 36)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: CACTIN NM_001080543.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210
• Publications: 15 publications found

Genes affected

CACTIN (HGNC:29938): (cactin, spliceosome C complex subunit) Enables RNA binding activity. Involved in several processes, including cellular response to cytokine stimulus; negative regulation of cytokine production; and negative regulation of signal transduction. Located in cytosol and nuclear speck. Part of catalytic step 2 spliceosome. [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 (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACTIN	NM_001080543.2	c.-162A>C		upstream_gene_variant		ENST00000429344.7	NP_001074012.1
CACTIN	NM_021231.2	c.-162A>C		upstream_gene_variant			NP_067054.1
CACTIN	XM_011528160.3	c.-162A>C		upstream_gene_variant			XP_011526462.1
CACTIN	XM_011528161.3	c.-162A>C		upstream_gene_variant			XP_011526463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACTIN	ENST00000429344.7	c.-162A>C		upstream_gene_variant		1	NM_001080543.2	ENSP00000415078.1
CACTIN	ENST00000221899.7	c.-162A>C		upstream_gene_variant		1		ENSP00000221899.4
CACTIN	ENST00000585942.5	n.-162A>C		upstream_gene_variant		1		ENSP00000465751.1
CACTIN	ENST00000248420.9	c.-162A>C		upstream_gene_variant		5		ENSP00000248420.5

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome AF: 0.00000219 AC: 1 AN: 456800 Hom.: 0 AF XY: 0.00000435 AC XY: 1 AN XY: 229670

African (AFR) AF: 0.00 AC: 0 AN: 10298

American (AMR) AF: 0.00 AC: 0 AN: 7742

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10802

East Asian (EAS) AF: 0.00 AC: 0 AN: 23696

South Asian (SAS) AF: 0.00 AC: 0 AN: 17958

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1770

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 337278

Other (OTH) AF: 0.0000425 AC: 1 AN: 23510

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.6
DANN	Benign	0.44
PhyloP100		-0.21
PromoterAI		-0.017	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2271875; hg19: chr19-3626922;