19-48469282-A-C

Position:

• chr19-48469282-A-C

Variant summary

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

The ENST00000427476(CYTH2):​c.-226A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 416,124 control chromosomes in the GnomAD database, including 135,914 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 0.75 (45329 hom., cov: 33)
  • Exomes 𝑓: 0.81 (90585 hom.)
• Consequence: CYTH2 ENST00000427476 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

Genes affected

CYTH2 (HGNC:9502): (cytohesin 2) The protein encoded by this gene is a member of the PSCD family. Members of this family have identical structural organization that consists of an N-terminal coiled-coil motif, a central Sec7 domain, and a C-terminal pleckstrin homology (PH) domain. The coiled-coil motif is involved in homodimerization, the Sec7 domain contains guanine-nucleotide exchange protein (GEP) activity, and the PH domain interacts with phospholipids and is responsible for association of PSCDs with membranes. Members of this family appear to mediate the regulation of protein sorting and membrane trafficking. The encoded protein exhibits GEP activity in vitro with ARF1, ARF3, and ARF6 and is 83% homologous to CYTH1. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

ENSG00000268465 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105372430	NR_186576.1	n.252T>G		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000268465	ENST00000595676.1	c.-29-1071A>C		intron_variant		2		ENSP00000470383.1

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114622 AN: 152016 Hom.: 45317 Cov.: 33

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.870

Gnomad AMR AF: 0.806

Gnomad ASJ AF: 0.890

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.844

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.877

Gnomad OTH AF: 0.755

GnomAD4 exome AF: 0.815 AC: 215112 AN: 263990 Hom.: 90585 Cov.: 4 AF XY: 0.819 AC XY: 109402 AN XY: 133642

Gnomad4 AFR exome AF: 0.521

Gnomad4 AMR exome AF: 0.816

Gnomad4 ASJ exome AF: 0.886

Gnomad4 EAS exome AF: 0.385

Gnomad4 SAS exome AF: 0.795

Gnomad4 FIN exome AF: 0.841

Gnomad4 NFE exome AF: 0.878

Gnomad4 OTH exome AF: 0.802

GnomAD4 genome AF: 0.754 AC: 114666 AN: 152134 Hom.: 45329 Cov.: 33 AF XY: 0.751 AC XY: 55847 AN XY: 74398

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.806

Gnomad4 ASJ AF: 0.890

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.800

Gnomad4 FIN AF: 0.844

Gnomad4 NFE AF: 0.877

Gnomad4 OTH AF: 0.755

Alfa AF: 0.849 Hom.: 84970

Bravo AF: 0.740

Asia WGS AF: 0.617 AC: 2148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.37

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: rs1799257; hg19: chr19-48972539; COSMIC: COSV57310270; COSMIC: COSV57310270;