rs3761026

Positions:

• chr19-1086044-T-C
• chr19-1086044-T-G

Variant summary

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

The NM_012292.5(ARHGAP45):​c.*38T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 1,549,448 control chromosomes in the GnomAD database, including 140,622 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 0.34 (10528 hom., cov: 32)
  • Exomes 𝑓: 0.42 (130094 hom.)
• Consequence: ARHGAP45 NM_012292.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

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]

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 (NFE) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP45	NM_012292.5	c.*38T>C		3_prime_UTR_variant	23/23	ENST00000313093.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP45	ENST00000313093.7	c.*38T>C		3_prime_UTR_variant	23/23	1	NM_012292.5	P3

Frequencies

GnomAD3 genomes AF: 0.342 AC: 52012 AN: 151920 Hom.: 10536 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.373

GnomAD3 exomes AF: 0.395 AC: 89181 AN: 225562 Hom.: 19117 AF XY: 0.397 AC XY: 48641 AN XY: 122476

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.458

Gnomad ASJ exome AF: 0.513

Gnomad EAS exome AF: 0.143

Gnomad SAS exome AF: 0.323

Gnomad FIN exome AF: 0.455

Gnomad NFE exome AF: 0.456

Gnomad OTH exome AF: 0.424

GnomAD4 exome AF: 0.424 AC: 592990 AN: 1397408 Hom.: 130094 Cov.: 24 AF XY: 0.422 AC XY: 293229 AN XY: 694486

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.451

Gnomad4 ASJ exome AF: 0.507

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.321

Gnomad4 FIN exome AF: 0.457

Gnomad4 NFE exome AF: 0.448

Gnomad4 OTH exome AF: 0.399

GnomAD4 genome AF: 0.342 AC: 51991 AN: 152040 Hom.: 10528 Cov.: 32 AF XY: 0.341 AC XY: 25305 AN XY: 74310

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.369

Alfa AF: 0.434 Hom.: 18939

Bravo AF: 0.333

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.095
DANN	Benign	0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3761026; hg19: chr19-1086043; COSMIC: COSV53125583; COSMIC: COSV53125583;