NM_020754.4:c.101-7674C>T

Variant names:

• chr3-119357642-C-T
• rs7614907
• NM_020754.4:c.101-7674C>T

Variant summary

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

The NM_020754.4(ARHGAP31):​c.101-7674C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0727 in 152,286 control chromosomes in the GnomAD database, including 553 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 0.073 (553 hom., cov: 33)
• Consequence: ARHGAP31 NM_020754.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.155 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP31	NM_020754.4	MANE Select	c.101-7674C>T		intron	N/A	NP_065805.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP31	ENST00000264245.9	TSL:1 MANE Select	c.101-7674C>T		intron	N/A	ENSP00000264245.4
	ARHGAP31	ENST00000861944.1		c.101-7674C>T		intron	N/A	ENSP00000532003.1
	ARHGAP31	ENST00000482743.1	TSL:4	c.14-7674C>T		intron	N/A	ENSP00000418429.1

Frequencies

GnomAD3 genomes AF: 0.0726 AC: 11049 AN: 152168 Hom.: 553 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0670

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.00211

Gnomad SAS AF: 0.0816

Gnomad FIN AF: 0.0414

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0476

Gnomad OTH AF: 0.0755

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

GnomAD4 genome AF: 0.0727 AC: 11072 AN: 152286 Hom.: 553 Cov.: 33 AF XY: 0.0717 AC XY: 5335 AN XY: 74454

African (AFR) AF: 0.101 AC: 4215 AN: 41538

American (AMR) AF: 0.161 AC: 2456 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 78 AN: 3472

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5194

South Asian (SAS) AF: 0.0823 AC: 397 AN: 4824

European-Finnish (FIN) AF: 0.0414 AC: 440 AN: 10618

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0476 AC: 3237 AN: 68024

Other (OTH) AF: 0.0752 AC: 159 AN: 2114

Alfa AF: 0.0544 Hom.: 573

Bravo AF: 0.0840

Asia WGS AF: 0.0550 AC: 192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.6
DANN	Benign	0.81
PhyloP100		0.20
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: rs7614907; hg19: chr3-119076489;