19-1085846-A-AGGACGGGGACGG

Position:

• chr19-1085846-A-AGGACGGGGACGG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BS1 BS2

The NM_012292.5(ARHGAP45):​c.3257_3268dupGGGACGGGGACG​(p.Gly1086_Asp1089dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000827 in 1,611,188 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0040 (5 hom., cov: 31)
  • Exomes 𝑓: 0.00050 (6 hom.)
• Consequence: ARHGAP45 NM_012292.5 disruptive_inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.35

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]

ARHGAP45 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_012292.5.
• BP6: Variant 19-1085846-A-AGGACGGGGACGG is Benign according to our data. Variant chr19-1085846-A-AGGACGGGGACGG is described in ClinVar as [Benign]. Clinvar id is 710671.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000497 (726/1460318) while in subpopulation AFR AF= 0.0183 (611/33342). AF 95% confidence interval is 0.0171. There are 6 homozygotes in gnomad4_exome. There are 283 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP45	NM_012292.5	c.3257_3268dupGGGACGGGGACG	p.Gly1086_Asp1089dup	disruptive_inframe_insertion	23/23	ENST00000313093.7	NP_036424.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP45	ENST00000313093.7	c.3257_3268dupGGGACGGGGACG	p.Gly1086_Asp1089dup	disruptive_inframe_insertion	23/23	1	NM_012292.5	ENSP00000316772.2

Frequencies

GnomAD3 genomes AF: 0.00401 AC: 604 AN: 150750 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000986

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00240

GnomAD3 exomes AF: 0.00102 AC: 253 AN: 247752 Hom.: 3 AF XY: 0.000763 AC XY: 103 AN XY: 134912

Gnomad AFR exome AF: 0.0151

Gnomad AMR exome AF: 0.000319

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000448

Gnomad OTH exome AF: 0.000657

GnomAD4 exome AF: 0.000497 AC: 726 AN: 1460318 Hom.: 6 Cov.: 31 AF XY: 0.000390 AC XY: 283 AN XY: 726508

Gnomad4 AFR exome AF: 0.0183

Gnomad4 AMR exome AF: 0.000559

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000243

Gnomad4 OTH exome AF: 0.000878

GnomAD4 genome AF: 0.00402 AC: 607 AN: 150870 Hom.: 5 Cov.: 31 AF XY: 0.00424 AC XY: 313 AN XY: 73788

Gnomad4 AFR AF: 0.0145

Gnomad4 AMR AF: 0.000984

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00237

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 04, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs201348186; hg19: chr19-1085845;