19-3626924-T-C

Variant names:

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

Variant summary

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

The NM_001080543.2(CACTIN):​c.-162A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 607,984 control chromosomes in the GnomAD database, including 124,511 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 0.68 (35447 hom., cov: 36)
  • Exomes 𝑓: 0.62 (89064 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080543.2. 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
	CACTIN	NM_001080543.2	MANE Select	c.-162A>G		upstream_gene	N/A	NP_001074012.1	Q8WUQ7-1
	CACTIN	NM_021231.2		c.-162A>G		upstream_gene	N/A	NP_067054.1	Q8WUQ7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACTIN	ENST00000429344.7	TSL:1 MANE Select	c.-162A>G		upstream_gene	N/A	ENSP00000415078.1	Q8WUQ7-1
	CACTIN	ENST00000221899.7	TSL:1	c.-162A>G		upstream_gene	N/A	ENSP00000221899.4	Q8WUQ7-1
	CACTIN	ENST00000585942.5	TSL:1	n.-162A>G		upstream_gene	N/A	ENSP00000465751.1	Q8WUQ7-1

Frequencies

GnomAD3 genomes AF: 0.677 AC: 103048 AN: 152130 Hom.: 35408 Cov.: 36

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.682

GnomAD4 exome AF: 0.622 AC: 283329 AN: 455736 Hom.: 89064 AF XY: 0.621 AC XY: 142241 AN XY: 229106

African (AFR) AF: 0.794 AC: 8159 AN: 10282

American (AMR) AF: 0.706 AC: 5465 AN: 7742

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 7034 AN: 10780

East Asian (EAS) AF: 0.589 AC: 13962 AN: 23690

South Asian (SAS) AF: 0.590 AC: 10569 AN: 17916

European-Finnish (FIN) AF: 0.656 AC: 15570 AN: 23732

Middle Eastern (MID) AF: 0.696 AC: 1230 AN: 1766

European-Non Finnish (NFE) AF: 0.613 AC: 206275 AN: 336358

Other (OTH) AF: 0.642 AC: 15065 AN: 23470

GnomAD4 genome AF: 0.677 AC: 103140 AN: 152248 Hom.: 35447 Cov.: 36 AF XY: 0.678 AC XY: 50437 AN XY: 74428

African (AFR) AF: 0.800 AC: 33241 AN: 41572

American (AMR) AF: 0.684 AC: 10471 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2269 AN: 3472

East Asian (EAS) AF: 0.596 AC: 3081 AN: 5166

South Asian (SAS) AF: 0.584 AC: 2820 AN: 4826

European-Finnish (FIN) AF: 0.663 AC: 7024 AN: 10600

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.619 AC: 42117 AN: 67996

Other (OTH) AF: 0.676 AC: 1426 AN: 2110

Alfa AF: 0.643 Hom.: 125256

Bravo AF: 0.687

Asia WGS AF: 0.602 AC: 2095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.9
DANN	Benign	0.50
PhyloP100		-0.21
PromoterAI		-0.053	Neutral

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2271875;

hg19: chr19-3626922;