NM_020754.4:c.1069+688T>G

Variant names:

• chr3-119399949-T-G
• rs11712165
• NM_020754.4:c.1069+688T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020754.4(ARHGAP31):​c.1069+688T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 152,062 control chromosomes in the GnomAD database, including 8,573 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (8573 hom., cov: 32)
• Consequence: ARHGAP31 NM_020754.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.788
• Publications: 41 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

LOC124906273 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020754.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP31	NM_020754.4	MANE Select	c.1069+688T>G		intron	N/A	NP_065805.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP31	ENST00000264245.9	TSL:1 MANE Select	c.1069+688T>G		intron	N/A	ENSP00000264245.4

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46130 AN: 151942 Hom.: 8568 Cov.: 32

Gnomad AFR AF: 0.0781

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.316

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.303 AC: 46146 AN: 152062 Hom.: 8573 Cov.: 32 AF XY: 0.308 AC XY: 22875 AN XY: 74330

African (AFR) AF: 0.0780 AC: 3239 AN: 41522

American (AMR) AF: 0.378 AC: 5778 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1278 AN: 3472

East Asian (EAS) AF: 0.412 AC: 2131 AN: 5172

South Asian (SAS) AF: 0.327 AC: 1574 AN: 4812

European-Finnish (FIN) AF: 0.427 AC: 4504 AN: 10538

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.388 AC: 26387 AN: 67958

Other (OTH) AF: 0.314 AC: 662 AN: 2110

Alfa AF: 0.368 Hom.: 42662

Bravo AF: 0.294

Asia WGS AF: 0.318 AC: 1106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.7
DANN	Benign	0.80
PhyloP100		0.79
Mutation Taster		=99/1	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: rs11712165; hg19: chr3-119118796;