Genetic Variant ARHGAP1:c.-170A>G (chr11-46700671-T-C) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

57 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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

African (AFR)

AF:

0.198

AC:

1422

AN:

7176

American (AMR)

AF:

0.549

AC:

4683

AN:

8526

Ashkenazi Jewish (ASJ)

AF:

0.740

AC:

5368

AN:

7256

East Asian (EAS)

AF:

0.295

AC:

4890

AN:

16562

South Asian (SAS)

AF:

0.642

AC:

15650

AN:

24368

European-Finnish (FIN)

AF:

0.641

AC:

10631

AN:

16594

Middle Eastern (MID)

AF:

0.681

AC:

735

AN:

1080

European-Non Finnish (NFE)

AF:

0.700

AC:

102561

AN:

146448

Other (OTH)

AF:

0.636

AC:

8764

AN:

13784

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

2378

4755

7133

9510

11888

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.536

AC:

81411

AN:

151972

Hom.:

25383

Cov.:

AF XY:

0.535

AC XY:

39733

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.208

AC:

8627

AN:

41420

American (AMR)

AF:

0.597

AC:

9109

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.742

AC:

2577

AN:

3472

East Asian (EAS)

AF:

0.311

AC:

1606

AN:

5158

South Asian (SAS)

AF:

0.664

AC:

3199

AN:

4816

European-Finnish (FIN)

AF:

0.627

AC:

6619

AN:

10560

Middle Eastern (MID)

AF:

0.656

AC:

193

AN:

294

European-Non Finnish (NFE)

AF:

0.701

AC:

47632

AN:

67966

Other (OTH)

AF:

0.603

AC:

1273

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1615

3229

4844

6458

8073

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.641

Hom.:

24798

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

(source)

DANN

Benign

0.85

PhyloP100

0.23

PromoterAI

0.00080

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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chr11-46700671-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over