chr19-3615409-G-A

Variant names:

• chr19-3615409-G-A
• rs768963
• NM_001080543.2:c.1163-820C>T

Variant summary

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

The NM_001080543.2(CACTIN):​c.1163-820C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 153,362 control chromosomes in the GnomAD database, including 20,424 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 0.50 (20180 hom., cov: 33)
  • Exomes 𝑓: 0.58 (244 hom.)
• Consequence: CACTIN NM_001080543.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.58
• Publications: 11 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.574 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACTIN	NM_001080543.2	MANE Select	c.1163-820C>T		intron	N/A	NP_001074012.1
	CACTIN	NM_021231.2		c.1163-820C>T		intron	N/A	NP_067054.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACTIN	ENST00000429344.7	TSL:1 MANE Select	c.1163-820C>T		intron	N/A	ENSP00000415078.1
	CACTIN	ENST00000221899.7	TSL:1	c.1163-820C>T		intron	N/A	ENSP00000221899.4
	CACTIN	ENST00000585942.5	TSL:1	n.1163-820C>T		intron	N/A	ENSP00000465751.1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76544 AN: 151928 Hom.: 20191 Cov.: 33

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.543

GnomAD4 exome AF: 0.580 AC: 763 AN: 1316 Hom.: 244 Cov.: 0 AF XY: 0.564 AC XY: 500 AN XY: 886

African (AFR) AF: 0.357 AC: 5 AN: 14

American (AMR) AF: 0.706 AC: 24 AN: 34

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 4 AN: 4

East Asian (EAS) AF: 0.167 AC: 3 AN: 18

South Asian (SAS) AF: 0.479 AC: 23 AN: 48

European-Finnish (FIN) AF: 0.617 AC: 58 AN: 94

Middle Eastern (MID) AF: 0.833 AC: 5 AN: 6

European-Non Finnish (NFE) AF: 0.590 AC: 604 AN: 1024

Other (OTH) AF: 0.500 AC: 37 AN: 74

GnomAD4 genome AF: 0.503 AC: 76555 AN: 152046 Hom.: 20180 Cov.: 33 AF XY: 0.505 AC XY: 37526 AN XY: 74320

African (AFR) AF: 0.355 AC: 14709 AN: 41436

American (AMR) AF: 0.584 AC: 8932 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1953 AN: 3470

East Asian (EAS) AF: 0.334 AC: 1723 AN: 5154

South Asian (SAS) AF: 0.422 AC: 2029 AN: 4810

European-Finnish (FIN) AF: 0.604 AC: 6403 AN: 10608

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.574 AC: 39006 AN: 67954

Other (OTH) AF: 0.536 AC: 1130 AN: 2108

Alfa AF: 0.524 Hom.: 2672

Bravo AF: 0.499

Asia WGS AF: 0.391 AC: 1363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.42
DANN	Benign	0.45
PhyloP100		-3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs768963; hg19: chr19-3615407; COSMIC: COSV50274017; COSMIC: COSV50274017;