2-227532850-T-G

Variant names:

• chr2-227532850-T-G
• rs6731443
• NM_004504.5:c.815-699T>G

Variant summary

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

The NM_004504.5(AGFG1):​c.815-699T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,918 control chromosomes in the GnomAD database, including 18,293 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 0.48 (18293 hom., cov: 32)
• Consequence: AGFG1 NM_004504.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.395
• Publications: 3 publications found

Genes affected

AGFG1 (HGNC:5175): (ArfGAP with FG repeats 1) The protein encoded by this gene is related to nucleoporins, a class of proteins that mediate nucleocytoplasmic transport. The encoded protein binds the activation domain of the human immunodeficiency virus Rev protein when Rev is assembled onto its RNA target, and is required for the nuclear export of Rev-directed RNAs. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• 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
AGFG1	NM_004504.5	c.815-699T>G		intron_variant	Intron 6 of 12	ENST00000310078.13	NP_004495.2
AGFG1	NM_001135187.2	c.886+641T>G		intron_variant	Intron 7 of 13		NP_001128659.1
AGFG1	NM_001135188.2	c.815-699T>G		intron_variant	Intron 6 of 12		NP_001128660.1
AGFG1	NM_001135189.2	c.695-699T>G		intron_variant	Intron 5 of 11		NP_001128661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGFG1	ENST00000310078.13	c.815-699T>G		intron_variant	Intron 6 of 12	1	NM_004504.5	ENSP00000312059.7

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72831 AN: 151800 Hom.: 18280 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.480 AC: 72863 AN: 151918 Hom.: 18293 Cov.: 32 AF XY: 0.480 AC XY: 35649 AN XY: 74230

African (AFR) AF: 0.315 AC: 13050 AN: 41456

American (AMR) AF: 0.533 AC: 8128 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1733 AN: 3468

East Asian (EAS) AF: 0.459 AC: 2373 AN: 5174

South Asian (SAS) AF: 0.637 AC: 3073 AN: 4824

European-Finnish (FIN) AF: 0.507 AC: 5348 AN: 10546

Middle Eastern (MID) AF: 0.521 AC: 151 AN: 290

European-Non Finnish (NFE) AF: 0.551 AC: 37443 AN: 67900

Other (OTH) AF: 0.498 AC: 1047 AN: 2102

Alfa AF: 0.423 Hom.: 1611

Bravo AF: 0.472

Asia WGS AF: 0.519 AC: 1799 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.70
PhyloP100		0.40
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: rs6731443; hg19: chr2-228397566;