Variant 19-1085691-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_012292.5(ARHGAP45):c.3096G>A(p.Ser1032Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,590,752 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 7 hom., cov: 31)

Exomes 𝑓: 0.00078 ( 12 hom. )

Consequence

ARHGAP45
NM_012292.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.77

Variant links:

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 links:

ARHGAP45 (HGNC:):

ARHGAP45 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 19-1085691-G-A is Benign according to our data. Variant chr19-1085691-G-A is described in ClinVar as [Benign]. Clinvar id is 717572.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.77 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00722 (1086/150314) while in subpopulation AFR AF= 0.0251 (1029/41002). AF 95% confidence interval is 0.0238. There are 7 homozygotes in gnomad4. There are 498 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP45	NM_012292.5 linkuse as main transcript	c.3096G>A	p.Ser1032Ser	synonymous_variant	23/23	ENST00000313093.7	NP_036424.2	Q92619-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP45	ENST00000313093.7 linkuse as main transcript	c.3096G>A	p.Ser1032Ser	synonymous_variant	23/23	1	NM_012292.5	ENSP00000316772.2		Q92619-1

Frequencies

GnomAD3 genomes

AF:

0.00722

AC:

1085

AN:

150190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0251

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00194

Gnomad ASJ

AF:

0.00174

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000213

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000148

Gnomad OTH

AF:

0.00532

GnomAD3 exomes

AF:

0.00182

AC:

425

AN:

234088

Hom.:

AF XY:

0.00150

AC XY:

193

AN XY:

128540

show subpopulations

Gnomad AFR exome

AF:

0.0252

Gnomad AMR exome

AF:

0.00126

Gnomad ASJ exome

AF:

0.00108

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000102

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.000352

GnomAD4 exome

AF:

0.000781

AC:

1125

AN:

1440438

Hom.:

Cov.:

AF XY:

0.000680

AC XY:

485

AN XY:

713516

show subpopulations

Gnomad4 AFR exome

AF:

0.0254

Gnomad4 AMR exome

AF:

0.00122

Gnomad4 ASJ exome

AF:

0.00106

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000129

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000692

Gnomad4 OTH exome

AF:

0.00179

GnomAD4 genome

AF:

0.00722

AC:

1086

AN:

150314

Hom.:

Cov.:

AF XY:

0.00679

AC XY:

498

AN XY:

73356

show subpopulations

Gnomad4 AFR

AF:

0.0251

Gnomad4 AMR

AF:

0.00193

Gnomad4 ASJ

AF:

0.00174

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000213

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000148

Gnomad4 OTH

AF:

0.00526

Alfa

AF:

0.00311

Hom.:

Bravo

AF:

0.00837

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.0060

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over