rs3761026

Variant names:

• chr19-1086044-T-C
• rs3761026
• NM_012292.5:c.*38T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012292.5. 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
	ARHGAP45	NM_012292.5	MANE Select	c.*38T>C		3_prime_UTR	Exon 23 of 23	NP_036424.2
	ARHGAP45	NM_001258328.4		c.*38T>C		3_prime_UTR	Exon 23 of 23	NP_001245257.1
	ARHGAP45	NM_001321232.2		c.*38T>C		3_prime_UTR	Exon 23 of 23	NP_001308161.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP45	ENST00000313093.7	TSL:1 MANE Select	c.*38T>C		3_prime_UTR	Exon 23 of 23	ENSP00000316772.2
	ARHGAP45	ENST00000586866.5	TSL:1	c.*38T>C		3_prime_UTR	Exon 23 of 23	ENSP00000468615.1
	ARHGAP45	ENST00000587602.5	TSL:2	n.*3019T>C		non_coding_transcript_exon	Exon 21 of 21	ENSP00000466365.1

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

GnomAD2 exomes AF: 0.395 AC: 89181 AN: 225562 AF XY: 0.397

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 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

African (AFR) AF: 0.122 AC: 3928 AN: 32222

American (AMR) AF: 0.451 AC: 19573 AN: 43430

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 12232 AN: 24108

East Asian (EAS) AF: 0.145 AC: 5694 AN: 39212

South Asian (SAS) AF: 0.321 AC: 26136 AN: 81368

European-Finnish (FIN) AF: 0.457 AC: 23201 AN: 50748

Middle Eastern (MID) AF: 0.498 AC: 2743 AN: 5512

European-Non Finnish (NFE) AF: 0.448 AC: 476277 AN: 1062710

Other (OTH) AF: 0.399 AC: 23206 AN: 58098

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

African (AFR) AF: 0.130 AC: 5406 AN: 41502

American (AMR) AF: 0.419 AC: 6406 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1765 AN: 3470

East Asian (EAS) AF: 0.142 AC: 731 AN: 5164

South Asian (SAS) AF: 0.318 AC: 1535 AN: 4824

European-Finnish (FIN) AF: 0.446 AC: 4717 AN: 10568

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30264 AN: 67930

Other (OTH) AF: 0.369 AC: 776 AN: 2102

Alfa AF: 0.425 Hom.: 22809

Bravo AF: 0.333

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.095
DANN	Benign	0.36
PhyloP100		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs3761026; hg19: chr19-1086043; COSMIC: COSV53125583; COSMIC: COSV53125583;