chr19-1086044-T-C

Variant names:

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

Variant summary

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

The NM_001258328.4(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_001258328.4 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]

POLR2E (HGNC:9192): (RNA polymerase II, I and III subunit E) This gene encodes the fifth largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. This subunit is shared by the other two DNA-directed RNA polymerases and is present in two-fold molar excess over the other polymerase subunits. An interaction between this subunit and a hepatitis virus transactivating protein has been demonstrated, suggesting that interaction between transcriptional activators and the polymerase can occur through this subunit. A pseudogene is located on chromosome 11. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

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_001258328.4. 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.*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

Sel.	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	ENST00000885660.1		c.*38T>C		3_prime_UTR	Exon 22 of 22	ENSP00000555719.1

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;