3-119406975-T-C

Variant names:

• chr3-119406975-T-C
• rs11922594
• NM_020754.4:c.1646-2521T>C

Variant summary

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

The NM_020754.4(ARHGAP31):​c.1646-2521T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 151,934 control chromosomes in the GnomAD database, including 27,962 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 0.60 (27962 hom., cov: 31)
• Consequence: ARHGAP31 NM_020754.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.216
• Publications: 9 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 (AFR) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP31	NM_020754.4	c.1646-2521T>C		intron_variant	Intron 10 of 11	ENST00000264245.9	NP_065805.2
LOC124906273	XR_007096027.1	n.2553A>G		non_coding_transcript_exon_variant	Exon 1 of 2
ARHGAP31	XM_006713714.4	c.1586-2521T>C		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.1646-2521T>C		intron_variant	Intron 10 of 11	1	NM_020754.4	ENSP00000264245.4

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91447 AN: 151816 Hom.: 27934 Cov.: 31

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.602 AC: 91529 AN: 151934 Hom.: 27962 Cov.: 31 AF XY: 0.607 AC XY: 45061 AN XY: 74276

African (AFR) AF: 0.698 AC: 28893 AN: 41382

American (AMR) AF: 0.596 AC: 9106 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1801 AN: 3470

East Asian (EAS) AF: 0.516 AC: 2671 AN: 5178

South Asian (SAS) AF: 0.616 AC: 2963 AN: 4808

European-Finnish (FIN) AF: 0.663 AC: 6979 AN: 10534

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37187 AN: 67954

Other (OTH) AF: 0.591 AC: 1248 AN: 2112

Alfa AF: 0.564 Hom.: 24507

Bravo AF: 0.600

Asia WGS AF: 0.575 AC: 2002 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	5.4
DANN	Benign	0.78
PhyloP100		0.22
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: rs11922594; hg19: chr3-119125822;