rs4663627

Variant names:

• chr2-235887904-C-T
• rs4663627
• NM_001037131.3:c.1155+4455C>T

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+4455C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 151,992 control chromosomes in the GnomAD database, including 9,907 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 0.34 (9907 hom., cov: 32)
• Consequence: AGAP1 NM_001037131.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGAP1	NM_001037131.3	c.1155+4455C>T		intron_variant	Intron 10 of 17	ENST00000304032.13	NP_001032208.1
AGAP1	NM_001436125.1	c.1950+4455C>T		intron_variant	Intron 10 of 17		NP_001423054.1
AGAP1	NM_001436126.1	c.1950+4455C>T		intron_variant	Intron 10 of 16		NP_001423055.1
AGAP1	NM_014914.5	c.1155+4455C>T		intron_variant	Intron 10 of 16		NP_055729.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGAP1	ENST00000304032.13	c.1155+4455C>T		intron_variant	Intron 10 of 17	5	NM_001037131.3	ENSP00000307634.7

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52100 AN: 151872 Hom.: 9901 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.343 AC: 52118 AN: 151992 Hom.: 9907 Cov.: 32 AF XY: 0.342 AC XY: 25399 AN XY: 74294

African (AFR) AF: 0.193 AC: 7997 AN: 41458

American (AMR) AF: 0.324 AC: 4950 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1373 AN: 3472

East Asian (EAS) AF: 0.561 AC: 2890 AN: 5150

South Asian (SAS) AF: 0.637 AC: 3058 AN: 4804

European-Finnish (FIN) AF: 0.344 AC: 3635 AN: 10568

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26981 AN: 67948

Other (OTH) AF: 0.358 AC: 754 AN: 2108

Alfa AF: 0.370 Hom.: 13153

Bravo AF: 0.333

Asia WGS AF: 0.557 AC: 1936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.71
DANN	Benign	0.72
PhyloP100		-1.2
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: rs4663627; hg19: chr2-236796548;