rs201348186

Variant names:

• chr19-1085846-AGGACGG-A
• rs201348186
• NM_012292.5:c.3263_3268delGGGACG

Your query was ambiguous. Multiple possible variants found:

• chr19-1085846-AGGACGG-A
• chr19-1085846-AGGACGG-AGGACGGGGACGG
• chr19-1085846-AGGACGG-AGGACGGGGACGGGGACGG
• chr19-1085846-AGGACGG-AGGACGGGGACGGGGACGGGGACGG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_012292.5(ARHGAP45):​c.3263_3268delGGGACG​(p.Gly1088_Asp1089del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000241 in 1,611,072 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00038 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: ARHGAP45 NM_012292.5 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_012292.5.

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.3263_3268delGGGACG	p.Gly1088_Asp1089del	disruptive_inframe_deletion	Exon 23 of 23	NP_036424.2
	ARHGAP45	NM_001258328.4		c.3311_3316delGGGACG	p.Gly1104_Asp1105del	disruptive_inframe_deletion	Exon 23 of 23	NP_001245257.1	Q92619-2
	ARHGAP45	NM_001321232.2		c.3275_3280delGGGACG	p.Gly1092_Asp1093del	disruptive_inframe_deletion	Exon 23 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.3263_3268delGGGACG	p.Gly1088_Asp1089del	disruptive_inframe_deletion	Exon 23 of 23	ENSP00000316772.2	Q92619-1
	ARHGAP45	ENST00000586866.5	TSL:1	c.3275_3280delGGGACG	p.Gly1092_Asp1093del	disruptive_inframe_deletion	Exon 23 of 23	ENSP00000468615.1	K7ES98
	ARHGAP45	ENST00000885660.1		c.3347_3352delGGGACG	p.Gly1116_Asp1117del	disruptive_inframe_deletion	Exon 22 of 22	ENSP00000555719.1

Frequencies

GnomAD3 genomes AF: 0.000378 AC: 57 AN: 150754 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000398

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000920

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000351 AC: 87 AN: 247752 AF XY: 0.000274

Gnomad AFR exome AF: 0.000327

Gnomad AMR exome AF: 0.00142

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000110

Gnomad FIN exome AF: 0.000324

Gnomad NFE exome AF: 0.000161

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000227 AC: 332 AN: 1460318 Hom.: 0 AF XY: 0.000204 AC XY: 148 AN XY: 726508

African (AFR) AF: 0.000240 AC: 8 AN: 33342

American (AMR) AF: 0.00139 AC: 62 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.000303 AC: 12 AN: 39606

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86236

European-Finnish (FIN) AF: 0.000248 AC: 13 AN: 52352

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5766

European-Non Finnish (NFE) AF: 0.000190 AC: 211 AN: 1111866

Other (OTH) AF: 0.000133 AC: 8 AN: 60344

GnomAD4 genome AF: 0.000378 AC: 57 AN: 150754 Hom.: 1 Cov.: 31 AF XY: 0.000421 AC XY: 31 AN XY: 73660

African (AFR) AF: 0.000398 AC: 16 AN: 40160

American (AMR) AF: 0.000920 AC: 14 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5152

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68006

Other (OTH) AF: 0.00144 AC: 3 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000438

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4
Mutation Taster		=165/35	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs201348186; hg19: chr19-1085845;