3-119365279-C-A

Variant names:

• chr3-119365279-C-A
• rs113568026
• NM_020754.4:c.101-37C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020754.4(ARHGAP31):​c.101-37C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.022 in 1,549,688 control chromosomes in the GnomAD database, including 557 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (47 hom., cov: 33)
  • Exomes 𝑓: 0.023 (510 hom.)
• Consequence: ARHGAP31 NM_020754.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0260
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 3-119365279-C-A is Benign according to our data. Variant chr3-119365279-C-A is described in ClinVar as [Benign]. Clinvar id is 1250667.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP31	NM_020754.4	c.101-37C>A		intron_variant	Intron 1 of 11	ENST00000264245.9	NP_065805.2
ARHGAP31	XM_006713714.4	c.101-37C>A		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	c.101-37C>A		intron_variant	Intron 1 of 11	1	NM_020754.4	ENSP00000264245.4
ARHGAP31	ENST00000482743.1	c.14-37C>A		intron_variant	Intron 1 of 5	4		ENSP00000418429.1

Frequencies

GnomAD3 genomes AF: 0.0172 AC: 2622 AN: 152110 Hom.: 47 Cov.: 33

Gnomad AFR AF: 0.00328

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00511

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.0610

Gnomad SAS AF: 0.0425

Gnomad FIN AF: 0.0484

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0191

Gnomad OTH AF: 0.0158

GnomAD2 exomes AF: 0.0236 AC: 5646 AN: 238784 AF XY: 0.0253

Gnomad AFR exome AF: 0.00249

Gnomad AMR exome AF: 0.00436

Gnomad ASJ exome AF: 0.0107

Gnomad EAS exome AF: 0.0624

Gnomad FIN exome AF: 0.0441

Gnomad NFE exome AF: 0.0198

Gnomad OTH exome AF: 0.0260

GnomAD4 exome AF: 0.0226 AC: 31517 AN: 1397460 Hom.: 510 Cov.: 23 AF XY: 0.0233 AC XY: 16269 AN XY: 698788

African (AFR) AF: 0.00375 AC: 120 AN: 32040

American (AMR) AF: 0.00449 AC: 200 AN: 44536

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 288 AN: 25766

East Asian (EAS) AF: 0.0753 AC: 2938 AN: 39012

South Asian (SAS) AF: 0.0379 AC: 3211 AN: 84670

European-Finnish (FIN) AF: 0.0463 AC: 2269 AN: 49032

Middle Eastern (MID) AF: 0.0108 AC: 61 AN: 5648

European-Non Finnish (NFE) AF: 0.0200 AC: 21161 AN: 1058460

Other (OTH) AF: 0.0218 AC: 1269 AN: 58296

GnomAD4 genome AF: 0.0172 AC: 2622 AN: 152228 Hom.: 47 Cov.: 33 AF XY: 0.0184 AC XY: 1369 AN XY: 74424

African (AFR) AF: 0.00327 AC: 136 AN: 41542

American (AMR) AF: 0.00510 AC: 78 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 36 AN: 3472

East Asian (EAS) AF: 0.0607 AC: 315 AN: 5188

South Asian (SAS) AF: 0.0427 AC: 206 AN: 4822

European-Finnish (FIN) AF: 0.0484 AC: 513 AN: 10590

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.0191 AC: 1302 AN: 68006

Other (OTH) AF: 0.0161 AC: 34 AN: 2114

Alfa AF: 0.0107 Hom.: 0

Bravo AF: 0.0134

Asia WGS AF: 0.0490 AC: 172 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 16, 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	-0.51
CADD	Benign	7.5
DANN	Benign	0.53
PhyloP100		-0.026
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs113568026; hg19: chr3-119084126;