Genetic Variant ARHGAP1:c.-50+178A>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 ENST00000917227.1(ARHGAP1):c.-50+178A>G variant causes a intron 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
ENST00000917227.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.233

Publications

58 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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000917227.1. 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
	ARHGAP1	NM_004308.5	MANE Select	c.-170A>G		upstream_gene	N/A	NP_004299.1	Q07960

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARHGAP1	ENST00000917227.1		c.-50+178A>G	intron	N/A	ENSP00000587286.1
ARHGAP1	ENST00000311956.9	TSL:1 MANE Select	c.-170A>G	upstream_gene	N/A	ENSP00000310491.4	Q07960
ARHGAP1	ENST00000524594.1	TSL:1	n.-56A>G	upstream_gene	N/A

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

Age Distribution

Exome Het

Exome Hom

Variant carriers

408

816

1224

1632

2040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Age Distribution

Genome Het

Genome Hom

Variant carriers

680

1360

2040

2720

3400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.641

Hom.:

24798

Bravo

AF:

0.516

Asia WGS

AF:

0.533

AC:

1855

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over