19-3615409-G-A

Position:

• chr19-3615409-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACTIN	NM_001080543.2	c.1163-820C>T		intron_variant		ENST00000429344.7	NP_001074012.1
CACTIN	XM_011528161.3	c.*2421C>T		3_prime_UTR_variant	7/7		XP_011526463.1
CACTIN	NM_021231.2	c.1163-820C>T		intron_variant			NP_067054.1
CACTIN	XM_011528160.3	c.1163-820C>T		intron_variant			XP_011526462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACTIN	ENST00000429344.7	c.1163-820C>T		intron_variant		1	NM_001080543.2	ENSP00000415078	P1

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

Gnomad4 AFR exome AF: 0.357

Gnomad4 AMR exome AF: 0.706

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.479

Gnomad4 FIN exome AF: 0.617

Gnomad4 NFE exome AF: 0.590

Gnomad4 OTH exome AF: 0.500

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

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.604

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.536

Alfa AF: 0.530 Hom.: 2624

Bravo AF: 0.499

Asia WGS AF: 0.391 AC: 1363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.42
DANN	Benign	0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

Publications

LitVar

Other links and lift over

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