chr3-119294711-G-C

Variant names:

• chr3-119294711-G-C
• rs4687994
• NM_020754.4:c.-194G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020754.4(ARHGAP31):​c.-194G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARHGAP31 NM_020754.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324
• Publications: 7 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP31	NM_020754.4	c.-194G>C		5_prime_UTR_variant	Exon 1 of 12	ENST00000264245.9	NP_065805.2
ARHGAP31	XM_006713714.4	c.-194G>C		5_prime_UTR_variant	Exon 1 of 12		XP_006713777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP31	ENST00000264245.9	c.-194G>C		5_prime_UTR_variant	Exon 1 of 12	1	NM_020754.4	ENSP00000264245.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000211 AC: 1 AN: 474242 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 252818

African (AFR) AF: 0.00 AC: 0 AN: 12874

American (AMR) AF: 0.00 AC: 0 AN: 21712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14428

East Asian (EAS) AF: 0.0000319 AC: 1 AN: 31386

South Asian (SAS) AF: 0.00 AC: 0 AN: 49686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2044

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 284994

Other (OTH) AF: 0.00 AC: 0 AN: 26974

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 1847

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	13
DANN	Benign	0.84
PhyloP100		-0.32
PromoterAI		-0.060	Neutral

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: rs4687994; hg19: chr3-119013558;