Genetic Variant NM_004308.5:c.-170A>G (chr11-46700671-T-C) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4BP6_Very_StrongBA1

The NM_004308.5(ARHGAP1):c.-170A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 393,766 control chromosomes in the GnomAD database, including 77,556 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 25383 hom., cov: 32)

Exomes 𝑓: 0.64 ( 52173 hom. )

Consequence

ARHGAP1
NM_004308.5 upstream_gene

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.233

Variant links:

Genes affected

ARHGAP1 (HGNC:673): (Rho GTPase activating protein 1) This gene encodes a member of a large family of proteins that activate Rho-type guanosine triphosphate (GTP) metabolizing enzymes. The encoded protein contains a SRC homology 3 domain and interacts with Bcl-2-associated protein family members. [provided by RefSeq, Aug 2012]

ARHGAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.18).

BP6

Variant 11-46700671-T-C is Benign according to our data. Variant chr11-46700671-T-C is described in ClinVar as [Benign]. Clinvar id is 1276936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
ARHGAP1	NM_004308.5 link	c.-170A>G	upstream_gene_variant	ENST00000311956.9	NP_004299.1	Q07960
ARHGAP1	XM_047426933.1 link	c.-129A>G	upstream_gene_variant		XP_047282889.1
ARHGAP1	XM_024448520.2 link	c.-170A>G	upstream_gene_variant		XP_024304288.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
ARHGAP1	ENST00000311956.9 link	c.-170A>G	upstream_gene_variant	1	NM_004308.5	ENSP00000310491.4	Q07960
ARHGAP1	ENST00000524594.1 link	n.-56A>G	upstream_gene_variant	1
ARHGAP1	ENST00000529960.5 link	n.-68A>G	upstream_gene_variant	1

Frequencies

GnomAD3 genomes

AF:

0.536

AC:

81400

AN:

151854

Hom.:

25376

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.634

Gnomad AMR

AF:

0.597

Gnomad ASJ

AF:

0.742

Gnomad EAS

AF:

0.312

Gnomad SAS

AF:

0.664

Gnomad FIN

AF:

0.627

Gnomad MID

AF:

0.655

Gnomad NFE

AF:

0.701

Gnomad OTH

AF:

0.596

GnomAD4 exome

AF:

0.640

AC:

154704

AN:

241794

Hom.:

52173

Cov.:

AF XY:

0.643

AC XY:

82355

AN XY:

128040

show subpopulations

Gnomad4 AFR exome

AF:

0.198

Gnomad4 AMR exome

AF:

0.549

Gnomad4 ASJ exome

AF:

0.740

Gnomad4 EAS exome

AF:

0.295

Gnomad4 SAS exome

AF:

0.642

Gnomad4 FIN exome

AF:

0.641

Gnomad4 NFE exome

AF:

0.700

Gnomad4 OTH exome

AF:

0.636

GnomAD4 genome

AF:

0.536

AC:

81411

AN:

151972

Hom.:

25383

Cov.:

AF XY:

0.535

AC XY:

39733

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.208

Gnomad4 AMR

AF:

0.597

Gnomad4 ASJ

AF:

0.742

Gnomad4 EAS

AF:

0.311

Gnomad4 SAS

AF:

0.664

Gnomad4 FIN

AF:

0.627

Gnomad4 NFE

AF:

0.701

Gnomad4 OTH

AF:

0.603

Alfa

AF:

0.660

Hom.:

9841

Bravo

AF:

0.516

Asia WGS

AF:

0.533

AC:

1855

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 16, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Benign

0.85

Splicing

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