19-3617421-C-G

Position:

• chr19-3617421-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080543.2(CACTIN):​c.1162+1454G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 152,194 control chromosomes in the GnomAD database, including 19,988 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 (19988 hom., cov: 34)
• Consequence: CACTIN NM_001080543.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.71

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]

CACTIN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACTIN	NM_001080543.2	c.1162+1454G>C		intron_variant		ENST00000429344.7	NP_001074012.1
CACTIN	XM_011528161.3	c.*409G>C		3_prime_UTR_variant	7/7		XP_011526463.1
CACTIN	NM_021231.2	c.1162+1454G>C		intron_variant			NP_067054.1
CACTIN	XM_011528160.3	c.1162+1454G>C		intron_variant			XP_011526462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACTIN	ENST00000429344.7	c.1162+1454G>C		intron_variant		1	NM_001080543.2	ENSP00000415078.1

Frequencies

GnomAD3 genomes AF: 0.500 AC: 76055 AN: 152076 Hom.: 19998 Cov.: 34

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.539

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.500 AC: 76067 AN: 152194 Hom.: 19988 Cov.: 34 AF XY: 0.502 AC XY: 37317 AN XY: 74404

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.581

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.604

Gnomad4 NFE AF: 0.572

Gnomad4 OTH AF: 0.532

Alfa AF: 0.424 Hom.: 1277

Bravo AF: 0.495

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.10
DANN	Benign	0.39

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: rs2024131; hg19: chr19-3617419;