NM_012292.5:c.412T>C

Variant names:

• chr19-1068735-T-C
• rs3764653
• NM_012292.5:c.412T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_012292.5(ARHGAP45):​c.412T>C​(p.Leu138Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 1,610,260 control chromosomes in the GnomAD database, including 113,100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (13110 hom., cov: 32)
  • Exomes 𝑓: 0.37 (99990 hom.)
• Consequence: ARHGAP45 NM_012292.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.63
• Publications: 17 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 19-1068735-T-C is Benign according to our data. Variant chr19-1068735-T-C is described in ClinVar as Benign. ClinVar VariationId is 1262943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.63 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP45	NM_012292.5	MANE Select	c.412T>C	p.Leu138Leu	synonymous	Exon 2 of 23	NP_036424.2
	ARHGAP45	NM_001258328.4		c.460T>C	p.Leu154Leu	synonymous	Exon 2 of 23	NP_001245257.1	Q92619-2
	ARHGAP45	NM_001321232.2		c.424T>C	p.Leu142Leu	synonymous	Exon 2 of 23	NP_001308161.1	K7ES98

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP45	ENST00000313093.7	TSL:1 MANE Select	c.412T>C	p.Leu138Leu	synonymous	Exon 2 of 23	ENSP00000316772.2	Q92619-1
	ARHGAP45	ENST00000586866.5	TSL:1	c.424T>C	p.Leu142Leu	synonymous	Exon 2 of 23	ENSP00000468615.1	K7ES98
	ARHGAP45	ENST00000885660.1		c.412T>C	p.Leu138Leu	synonymous	Exon 2 of 22	ENSP00000555719.1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62129 AN: 151400 Hom.: 13077 Cov.: 32

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.391

GnomAD2 exomes AF: 0.379 AC: 90353 AN: 238622 AF XY: 0.376

Gnomad AFR exome AF: 0.526

Gnomad AMR exome AF: 0.418

Gnomad ASJ exome AF: 0.317

Gnomad EAS exome AF: 0.338

Gnomad FIN exome AF: 0.361

Gnomad NFE exome AF: 0.359

Gnomad OTH exome AF: 0.378

GnomAD4 exome AF: 0.368 AC: 536245 AN: 1458742 Hom.: 99990 Cov.: 40 AF XY: 0.368 AC XY: 266758 AN XY: 725614

African (AFR) AF: 0.517 AC: 17267 AN: 33416

American (AMR) AF: 0.421 AC: 18796 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 8238 AN: 26112

East Asian (EAS) AF: 0.356 AC: 14097 AN: 39648

South Asian (SAS) AF: 0.386 AC: 33277 AN: 86202

European-Finnish (FIN) AF: 0.361 AC: 18726 AN: 51906

Middle Eastern (MID) AF: 0.336 AC: 1936 AN: 5762

European-Non Finnish (NFE) AF: 0.362 AC: 401636 AN: 1110734

Other (OTH) AF: 0.369 AC: 22272 AN: 60306

GnomAD4 genome AF: 0.411 AC: 62208 AN: 151518 Hom.: 13110 Cov.: 32 AF XY: 0.412 AC XY: 30452 AN XY: 74000

African (AFR) AF: 0.523 AC: 21590 AN: 41244

American (AMR) AF: 0.413 AC: 6290 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1088 AN: 3464

East Asian (EAS) AF: 0.349 AC: 1796 AN: 5144

South Asian (SAS) AF: 0.365 AC: 1756 AN: 4808

European-Finnish (FIN) AF: 0.369 AC: 3876 AN: 10514

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24602 AN: 67808

Other (OTH) AF: 0.385 AC: 810 AN: 2102

Alfa AF: 0.380 Hom.: 5808

Bravo AF: 0.420

Asia WGS AF: 0.351 AC: 1217 AN: 3478

EpiCase AF: 0.363

EpiControl AF: 0.356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.4
DANN	Benign	0.78
PhyloP100		1.6
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: rs3764653; hg19: chr19-1068734; COSMIC: COSV54033847; COSMIC: COSV54033847;