NM_020754.4:c.1645+2034G>A

Variant names:

• chr3-119404431-G-A
• rs61579022
• NM_020754.4:c.1645+2034G>A

Variant summary

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

The NM_020754.4(ARHGAP31):​c.1645+2034G>A 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 152,094 control chromosomes in the GnomAD database, including 8,572 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 (8572 hom., cov: 31)
• Consequence: ARHGAP31 NM_020754.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120
• Publications: 13 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP31	NM_020754.4	c.1645+2034G>A		intron_variant	Intron 10 of 11	ENST00000264245.9	NP_065805.2
LOC124906273	XR_007096027.1	n.5097C>T		non_coding_transcript_exon_variant	Exon 1 of 2
ARHGAP31	XM_006713714.4	c.1585+2034G>A		intron_variant	Intron 10 of 11		XP_006713777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP31	ENST00000264245.9	c.1645+2034G>A		intron_variant	Intron 10 of 11	1	NM_020754.4	ENSP00000264245.4

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46113 AN: 151976 Hom.: 8567 Cov.: 31

Gnomad AFR AF: 0.0782

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.303 AC: 46129 AN: 152094 Hom.: 8572 Cov.: 31 AF XY: 0.308 AC XY: 22878 AN XY: 74360

African (AFR) AF: 0.0781 AC: 3245 AN: 41532

American (AMR) AF: 0.378 AC: 5779 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1277 AN: 3470

East Asian (EAS) AF: 0.409 AC: 2100 AN: 5140

South Asian (SAS) AF: 0.326 AC: 1571 AN: 4818

European-Finnish (FIN) AF: 0.428 AC: 4520 AN: 10568

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

European-Non Finnish (NFE) AF: 0.388 AC: 26384 AN: 67960

Other (OTH) AF: 0.313 AC: 661 AN: 2112

Alfa AF: 0.317 Hom.: 1096

Bravo AF: 0.294

Asia WGS AF: 0.318 AC: 1107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.32
PhyloP100		-0.012
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: rs61579022; hg19: chr3-119123278;