19-1065946-C-T

Position:

• chr19-1065946-C-T

Variant summary

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

The ENST00000539243(ARHGAP45):​c.-80C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,483,714 control chromosomes in the GnomAD database, including 28,530 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 0.17 (2699 hom., cov: 34)
  • Exomes 𝑓: 0.19 (25831 hom.)
• Consequence: ARHGAP45 ENST00000539243 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.26

Genes affected

ARHGAP45 (HGNC:17102): (Rho GTPase activating protein 45) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.1065946C>T		intergenic_region
ARHGAP45	NM_001258328.4	c.-80C>T		upstream_gene_variant			NP_001245257.1
ARHGAP45	XM_047438545.1	c.-80C>T		upstream_gene_variant			XP_047294501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP45	ENST00000539243	c.-80C>T		5_prime_UTR_premature_start_codon_gain_variant	1/23	2		ENSP00000439601.1
ARHGAP45	ENST00000539243	c.-80C>T		5_prime_UTR_variant	1/23	2		ENSP00000439601.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25420 AN: 152150 Hom.: 2689 Cov.: 34

Gnomad AFR AF: 0.0438

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.167

GnomAD4 exome AF: 0.191 AC: 254342 AN: 1331446 Hom.: 25831 Cov.: 31 AF XY: 0.193 AC XY: 125786 AN XY: 651744

Gnomad4 AFR exome AF: 0.0339

Gnomad4 AMR exome AF: 0.320

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.323

Gnomad4 SAS exome AF: 0.241

Gnomad4 FIN exome AF: 0.229

Gnomad4 NFE exome AF: 0.183

Gnomad4 OTH exome AF: 0.191

GnomAD4 genome AF: 0.167 AC: 25427 AN: 152268 Hom.: 2699 Cov.: 34 AF XY: 0.176 AC XY: 13090 AN XY: 74450

Gnomad4 AFR AF: 0.0437

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.164

Alfa AF: 0.177 Hom.: 2558

Bravo AF: 0.163

Asia WGS AF: 0.258 AC: 895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.40
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2242436; hg19: chr19-1065945; COSMIC: COSV54026600; COSMIC: COSV54026600;