Genetic Variant ARHGAP31:c.100+148delT (chr3-119295140-CT-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_020754.4(ARHGAP31):c.100+148delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 542,454 control chromosomes in the GnomAD database, including 10,512 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.28 ( 7082 hom., cov: 17)

Exomes 𝑓: 0.31 ( 3430 hom. )

Consequence

ARHGAP31
NM_020754.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0770

Publications

0 publications found

Variant links:

Genes affected

ARHGAP31 (HGNC:29216): (Rho GTPase activating protein 31) This gene encodes a GTPase-activating protein (GAP). A variety of cellular processes are regulated by Rho GTPases which cycle between an inactive form bound to GDP and an active form bound to GTP. This cycling between inactive and active forms is regulated by guanine nucleotide exchange factors and GAPs. The encoded protein is a GAP shown to regulate two GTPases involved in protein trafficking and cell growth. [provided by RefSeq, Jul 2008]

ARHGAP31 Gene-Disease associations (from GenCC):

Adams-Oliver syndrome 1
Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
Adams-Oliver syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ARHGAP31 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 3-119295140-CT-C is Benign according to our data. Variant chr3-119295140-CT-C is described in ClinVar as [Benign]. Clinvar id is 1290204.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP31	NM_020754.4 link	c.100+148delT		intron_variant	Intron 1 of 11	ENST00000264245.9	NP_065805.2	Q2M1Z3A0A8S0MHV1
ARHGAP31	XM_006713714.4 link	c.100+148delT		intron_variant	Intron 1 of 11		XP_006713777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP31	ENST00000264245.9 link	c.100+137delT		intron_variant	Intron 1 of 11	1	NM_020754.4	ENSP00000264245.4		Q2M1Z3

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

39523

AN:

139438

Hom.:

7060

Cov.:

show subpopulations

Gnomad AFR

AF:

0.533

Gnomad AMI

AF:

0.0731

Gnomad AMR

AF:

0.212

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.140

Gnomad SAS

AF:

0.275

Gnomad FIN

AF:

0.219

Gnomad MID

AF:

0.183

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.253

GnomAD4 exome

AF:

0.306

AC:

123471

AN:

402948

Hom.:

3430

AF XY:

0.311

AC XY:

66952

AN XY:

215368

show subpopulations

African (AFR)

AF:

0.503

AC:

5588

AN:

11102

American (AMR)

AF:

0.309

AC:

4840

AN:

15646

Ashkenazi Jewish (ASJ)

AF:

0.312

AC:

3855

AN:

12354

East Asian (EAS)

AF:

0.292

AC:

5712

AN:

19562

South Asian (SAS)

AF:

0.384

AC:

14427

AN:

37608

European-Finnish (FIN)

AF:

0.307

AC:

7608

AN:

24822

Middle Eastern (MID)

AF:

0.299

AC:

782

AN:

2616

European-Non Finnish (NFE)

AF:

0.285

AC:

73670

AN:

258124

Other (OTH)

AF:

0.331

AC:

6989

AN:

21114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

Heterozygous variant carriers

4522

9043

13565

18086

22608

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.284

AC:

39599

AN:

139506

Hom.:

7082

Cov.:

AF XY:

0.284

AC XY:

19130

AN XY:

67398

show subpopulations

African (AFR)

AF:

0.533

AC:

20635

AN:

38724

American (AMR)

AF:

0.212

AC:

2863

AN:

13484

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

560

AN:

3246

East Asian (EAS)

AF:

0.140

AC:

652

AN:

4664

South Asian (SAS)

AF:

0.276

AC:

1190

AN:

4318

European-Finnish (FIN)

AF:

0.219

AC:

1786

AN:

8148

Middle Eastern (MID)

AF:

0.194

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.177

AC:

11296

AN:

63856

Other (OTH)

AF:

0.260

AC:

500

AN:

1926

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1206

2412

3617

4823

6029

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0610

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 08, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.077

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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3-119295140-CT-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