2-235886699-A-C

Variant names:

• chr2-235886699-A-C
• rs13025591
• NM_001037131.3:c.1155+3250A>C

Variant summary

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

The NM_001037131.3(AGAP1):​c.1155+3250A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,060 control chromosomes in the GnomAD database, including 10,909 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 0.37 (10909 hom., cov: 33)
• Consequence: AGAP1 NM_001037131.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.525
• Publications: 21 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037131.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGAP1	NM_001037131.3	MANE Select	c.1155+3250A>C		intron	N/A	NP_001032208.1
	AGAP1	NM_001436125.1		c.1950+3250A>C		intron	N/A	NP_001423054.1
	AGAP1	NM_001436126.1		c.1950+3250A>C		intron	N/A	NP_001423055.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGAP1	ENST00000304032.13	TSL:5 MANE Select	c.1155+3250A>C		intron	N/A	ENSP00000307634.7
	AGAP1	ENST00000336665.9	TSL:1	c.1155+3250A>C		intron	N/A	ENSP00000338378.5
	AGAP1	ENST00000409538.5	TSL:5	c.1950+3250A>C		intron	N/A	ENSP00000386897.1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56412 AN: 151942 Hom.: 10903 Cov.: 33

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.371 AC: 56445 AN: 152060 Hom.: 10909 Cov.: 33 AF XY: 0.370 AC XY: 27506 AN XY: 74322

African (AFR) AF: 0.293 AC: 12144 AN: 41510

American (AMR) AF: 0.335 AC: 5117 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1376 AN: 3466

East Asian (EAS) AF: 0.538 AC: 2786 AN: 5176

South Asian (SAS) AF: 0.636 AC: 3063 AN: 4814

European-Finnish (FIN) AF: 0.345 AC: 3638 AN: 10552

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27046 AN: 67966

Other (OTH) AF: 0.374 AC: 789 AN: 2108

Alfa AF: 0.387 Hom.: 17943

Bravo AF: 0.365

Asia WGS AF: 0.547 AC: 1900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.18
DANN	Benign	0.80
PhyloP100		-0.53
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: rs13025591; hg19: chr2-236795343;