dbSNP rs17203055: ARHGAP31:c.203+66A>G (chr3-119365484-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020754.4(ARHGAP31):c.203+66A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,394,956 control chromosomes in the GnomAD database, including 9,614 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.098 ( 981 hom., cov: 32)

Exomes 𝑓: 0.11 ( 8633 hom. )

Consequence

ARHGAP31
NM_020754.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0770

Publications

8 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 3-119365484-A-G is Benign according to our data. Variant chr3-119365484-A-G is described in ClinVar as Benign. ClinVar VariationId is 1273175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP31	NM_020754.4 link	c.203+66A>G		intron_variant	Intron 2 of 11	ENST00000264245.9	NP_065805.2	Q2M1Z3A0A8S0MHV1
ARHGAP31	XM_006713714.4 link	c.203+66A>G		intron_variant	Intron 2 of 11		XP_006713777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP31	ENST00000264245.9 link	c.203+66A>G		intron_variant	Intron 2 of 11	1	NM_020754.4	ENSP00000264245.4		Q2M1Z3
ARHGAP31	ENST00000482743.1 link	c.116+66A>G		intron_variant	Intron 2 of 5	4		ENSP00000418429.1		C9J652

Frequencies

GnomAD3 genomes

AF:

0.0983

AC:

14957

AN:

152094

Hom.:

979

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0431

Gnomad AMI

AF:

0.182

Gnomad AMR

AF:

0.212

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0881

Gnomad FIN

AF:

0.108

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.114

GnomAD4 exome

AF:

0.109

AC:

136063

AN:

1242744

Hom.:

8633

AF XY:

0.108

AC XY:

67973

AN XY:

627546

show subpopulations

African (AFR)

AF:

0.0421

AC:

1205

AN:

28622

American (AMR)

AF:

0.272

AC:

11639

AN:

42718

Ashkenazi Jewish (ASJ)

AF:

0.126

AC:

3120

AN:

24796

East Asian (EAS)

AF:

0.000428

AC:

AN:

37394

South Asian (SAS)

AF:

0.0958

AC:

7701

AN:

80426

European-Finnish (FIN)

AF:

0.101

AC:

4832

AN:

47878

Middle Eastern (MID)

AF:

0.110

AC:

589

AN:

5362

European-Non Finnish (NFE)

AF:

0.110

AC:

101122

AN:

922302

Other (OTH)

AF:

0.110

AC:

5839

AN:

53246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

6262

12524

18786

25048

31310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3444

6888

10332

13776

17220

<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:

0.0984

AC:

14979

AN:

152212

Hom.:

981

Cov.:

AF XY:

0.0996

AC XY:

7414

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0433

AC:

1799

AN:

41542

American (AMR)

AF:

0.212

AC:

3243

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

443

AN:

3470

East Asian (EAS)

AF:

0.00116

AC:

AN:

5184

South Asian (SAS)

AF:

0.0888

AC:

428

AN:

4820

European-Finnish (FIN)

AF:

0.108

AC:

1140

AN:

10588

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.110

AC:

7473

AN:

67998

Other (OTH)

AF:

0.113

AC:

239

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

669

1339

2008

2678

3347

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

166

332

498

664

830

<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:

0.0958

Hom.:

630

Bravo

AF:

0.106

Asia WGS

AF:

0.0500

AC:

173

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

- -

Nov 08, 2018

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

-0.88

CADD

Benign

0.58

(source)

DANN

Benign

0.23

PhyloP100

-0.077

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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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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