2-235620294-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001037131.3(AGAP1):c.164-88885A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 151,526 control chromosomes in the GnomAD database, including 6,475 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 0.27 (6475 hom., cov: 32)
• Consequence: AGAP1 NM_001037131.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.711

Genes affected

AGAP1 (HGNC:16922): (ArfGAP with GTPase domain, ankyrin repeat and PH domain 1) This gene encodes a member of an ADP-ribosylation factor GTPase-activating protein family involved in membrane trafficking and cytoskeleton dynamics. This gene functions as a direct regulator of the adaptor-related protein complex 3 on endosomes. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGAP1	NM_001037131.3	c.164-88885A>T		intron_variant		ENST00000304032.13
AGAP1	NM_001244888.2	c.164-88885A>T		intron_variant
AGAP1	NM_014914.5	c.164-88885A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGAP1	ENST00000304032.13	c.164-88885A>T		intron_variant		5	NM_001037131.3

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41382 AN: 151406 Hom.: 6473 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.00352

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.273 AC: 41423 AN: 151526 Hom.: 6475 Cov.: 32 AF XY: 0.268 AC XY: 19819 AN XY: 74004

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.00353

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.281

Alfa AF: 0.249 Hom.: 615

Bravo AF: 0.279

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.67
Dann	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs10199178; hg19: chr2-236528938;