8-144552744-C-T

Variant names:

• chr8-144552744-C-T
• rs2620636
• NM_025251.3:c.596+2816G>A

Variant summary

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

The NM_025251.3(ARHGAP39):​c.596+2816G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,114 control chromosomes in the GnomAD database, including 1,402 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 0.10 (1402 hom., cov: 33)
• Consequence: ARHGAP39 NM_025251.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 6 publications found

Genes affected

ARHGAP39 (HGNC:29351): (Rho GTPase activating protein 39) Predicted to enable GTPase activator activity. Involved in postsynapse organization. Is active in glutamatergic synapse. [provided by Alliance of Genome Resources, Apr 2022]

ARHGAP39 Gene-Disease associations (from GenCC):

• central nervous system malformation

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025251.3. 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
	ARHGAP39	NM_025251.3	MANE Select	c.596+2816G>A		intron	N/A	NP_079527.1
	ARHGAP39	NM_001308207.1		c.596+2816G>A		intron	N/A	NP_001295136.1
	ARHGAP39	NM_001308208.2		c.596+2816G>A		intron	N/A	NP_001295137.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP39	ENST00000377307.7	TSL:5 MANE Select	c.596+2816G>A		intron	N/A	ENSP00000366522.2
	ARHGAP39	ENST00000905351.1		c.596+2816G>A		intron	N/A	ENSP00000575410.1
	ARHGAP39	ENST00000905352.1		c.596+2816G>A		intron	N/A	ENSP00000575411.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15400 AN: 151996 Hom.: 1392 Cov.: 33

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0999

Gnomad ASJ AF: 0.0930

Gnomad EAS AF: 0.00674

Gnomad SAS AF: 0.0886

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0426

Gnomad OTH AF: 0.0904

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

GnomAD4 genome AF: 0.102 AC: 15455 AN: 152114 Hom.: 1402 Cov.: 33 AF XY: 0.0998 AC XY: 7422 AN XY: 74386

African (AFR) AF: 0.238 AC: 9866 AN: 41448

American (AMR) AF: 0.100 AC: 1533 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0930 AC: 323 AN: 3472

East Asian (EAS) AF: 0.00675 AC: 35 AN: 5182

South Asian (SAS) AF: 0.0887 AC: 428 AN: 4826

European-Finnish (FIN) AF: 0.0136 AC: 144 AN: 10576

Middle Eastern (MID) AF: 0.0517 AC: 15 AN: 290

European-Non Finnish (NFE) AF: 0.0426 AC: 2898 AN: 68002

Other (OTH) AF: 0.0895 AC: 189 AN: 2112

Alfa AF: 0.0651 Hom.: 1095

Bravo AF: 0.115

Asia WGS AF: 0.0560 AC: 195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.17
DANN	Benign	0.19
PhyloP100		-1.7
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: rs2620636; hg19: chr8-145778128;