19-48469282-A-C

Variant names:

• chr19-48469282-A-C
• rs1799257
• ENST00000427476.4:c.-226A>C

Variant summary

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

The ENST00000427476.4(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 ENST00000427476.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000427476.4. 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
	LOC105372430	NR_186576.1		n.252T>G		non_coding_transcript_exon	Exon 1 of 3
	CYTH2	NM_004228.7	MANE Select	c.-226A>C		upstream_gene	N/A	NP_004219.3
	CYTH2	NM_017457.6		c.-226A>C		upstream_gene	N/A	NP_059431.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYTH2	ENST00000427476.4	TSL:1	c.-226A>C		5_prime_UTR	Exon 1 of 12	ENSP00000486578.1
	ENSG00000268465	ENST00000595676.1	TSL:2	c.-29-1071A>C		intron	N/A	ENSP00000470383.1
	ENSG00000268530	ENST00000593476.1	TSL:1	n.264+148T>G		intron	N/A

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

African (AFR) AF: 0.521 AC: 3812 AN: 7320

American (AMR) AF: 0.816 AC: 5935 AN: 7274

Ashkenazi Jewish (ASJ) AF: 0.886 AC: 8177 AN: 9232

East Asian (EAS) AF: 0.385 AC: 8730 AN: 22692

South Asian (SAS) AF: 0.795 AC: 2518 AN: 3166

European-Finnish (FIN) AF: 0.841 AC: 17235 AN: 20490

Middle Eastern (MID) AF: 0.779 AC: 1031 AN: 1324

European-Non Finnish (NFE) AF: 0.878 AC: 154253 AN: 175754

Other (OTH) AF: 0.802 AC: 13421 AN: 16738

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

African (AFR) AF: 0.527 AC: 21839 AN: 41442

American (AMR) AF: 0.806 AC: 12335 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 3086 AN: 3468

East Asian (EAS) AF: 0.450 AC: 2331 AN: 5178

South Asian (SAS) AF: 0.800 AC: 3860 AN: 4822

European-Finnish (FIN) AF: 0.844 AC: 8952 AN: 10606

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.877 AC: 59663 AN: 68000

Other (OTH) AF: 0.755 AC: 1597 AN: 2116

Alfa AF: 0.835 Hom.: 131735

Bravo AF: 0.740

Asia WGS AF: 0.617 AC: 2148 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	13
DANN	Benign	0.37
PhyloP100		1.2
PromoterAI		-0.068	Neutral
Mutation Taster		=300/0	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: rs1799257; hg19: chr19-48972539; COSMIC: COSV57310270; COSMIC: COSV57310270;