Variant 2-235494818-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_001037131.3(AGAP1):c.132C>T(p.Asn44=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 1,579,606 control chromosomes in the GnomAD database, including 749 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.020 ( 54 hom., cov: 29)

Exomes 𝑓: 0.028 ( 695 hom. )

Consequence

AGAP1
NM_001037131.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.48

Variant links:

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]

AGAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 2-235494818-C-T is Benign according to our data. Variant chr2-235494818-C-T is described in ClinVar as [Benign]. Clinvar id is 2013594.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=3.48 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0202 (3065/151520) while in subpopulation NFE AF= 0.0319 (2159/67760). AF 95% confidence interval is 0.0307. There are 54 homozygotes in gnomad4. There are 1382 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 54 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
AGAP1	NM_001037131.3 linkuse as main transcript	c.132C>T	p.Asn44=	synonymous_variant	1/18	ENST00000304032.13	NP_001032208.1
AGAP1	NM_014914.5 linkuse as main transcript	c.132C>T	p.Asn44=	synonymous_variant	1/17		NP_055729.2
AGAP1	NM_001244888.2 linkuse as main transcript	c.132C>T	p.Asn44=	synonymous_variant	1/10		NP_001231817.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGAP1	ENST00000304032.13 linkuse as main transcript	c.132C>T	p.Asn44=	synonymous_variant	1/18	5	NM_001037131.3	ENSP00000307634		Q9UPQ3-1

Frequencies

GnomAD3 genomes

AF:

0.0202

AC:

3064

AN:

151414

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00600

Gnomad AMI

AF:

0.0549

Gnomad AMR

AF:

0.0244

Gnomad ASJ

AF:

0.0168

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00456

Gnomad FIN

AF:

0.00880

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0319

Gnomad OTH

AF:

0.0283

GnomAD3 exomes

AF:

0.0189

AC:

4268

AN:

225286

Hom.:

AF XY:

0.0191

AC XY:

2346

AN XY:

123008

show subpopulations

Gnomad AFR exome

AF:

0.00500

Gnomad AMR exome

AF:

0.0147

Gnomad ASJ exome

AF:

0.0159

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00431

Gnomad FIN exome

AF:

0.00779

Gnomad NFE exome

AF:

0.0310

Gnomad OTH exome

AF:

0.0236

GnomAD4 exome

AF:

0.0278

AC:

39712

AN:

1428086

Hom.:

695

Cov.:

AF XY:

0.0272

AC XY:

19321

AN XY:

710374

show subpopulations

Gnomad4 AFR exome

AF:

0.00448

Gnomad4 AMR exome

AF:

0.0162

Gnomad4 ASJ exome

AF:

0.0159

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00463

Gnomad4 FIN exome

AF:

0.00963

Gnomad4 NFE exome

AF:

0.0330

Gnomad4 OTH exome

AF:

0.0227

GnomAD4 genome

AF:

0.0202

AC:

3065

AN:

151520

Hom.:

Cov.:

AF XY:

0.0187

AC XY:

1382

AN XY:

74078

show subpopulations

Gnomad4 AFR

AF:

0.00599

Gnomad4 AMR

AF:

0.0244

Gnomad4 ASJ

AF:

0.0168

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00478

Gnomad4 FIN

AF:

0.00880

Gnomad4 NFE

AF:

0.0319

Gnomad4 OTH

AF:

0.0280

Alfa

AF:

0.0257

Hom.:

Bravo

AF:

0.0217

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.98

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over