rs3769292

Positions:

• chr2-172861531-G-A
• chr2-172861531-G-C

Variant summary

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

The NM_007023.4(RAPGEF4):​c.444+47106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0957 in 152,226 control chromosomes in the GnomAD database, including 713 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 0.096 (713 hom., cov: 33)
• Consequence: RAPGEF4 NM_007023.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32

Genes affected

RAPGEF4 (HGNC:16626): (Rap guanine nucleotide exchange factor 4) Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of neurotransmitter receptor localization to postsynaptic specialization membrane and regulation of postsynapse organization. Predicted to act upstream of or within adenylate cyclase-activating G protein-coupled receptor signaling pathway; regulation of exocytosis; and secretion by cell. Predicted to be located in plasma membrane. Predicted to be active in glutamatergic synapse; hippocampal mossy fiber to CA3 synapse; and postsynaptic density. Implicated in autistic disorder. [provided by Alliance of Genome Resources, Apr 2022]

RAPGEF4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAPGEF4	NM_007023.4	c.444+47106G>A		intron_variant		ENST00000397081.8	NP_008954.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAPGEF4	ENST00000397081.8	c.444+47106G>A		intron_variant		1	NM_007023.4	ENSP00000380271.3
RAPGEF4	ENST00000409036.5	c.444+47106G>A		intron_variant		5		ENSP00000387104.1

Frequencies

GnomAD3 genomes AF: 0.0956 AC: 14537 AN: 152108 Hom.: 706 Cov.: 33

Gnomad AFR AF: 0.0863

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0682

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0955

Gnomad OTH AF: 0.0957

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

GnomAD4 genome AF: 0.0957 AC: 14563 AN: 152226 Hom.: 713 Cov.: 33 AF XY: 0.0965 AC XY: 7179 AN XY: 74428

Gnomad4 AFR AF: 0.0862

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.0682

Gnomad4 NFE AF: 0.0955

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0942 Hom.: 209

Bravo AF: 0.0954

Asia WGS AF: 0.163 AC: 568 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.1
DANN	Benign	0.37

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: rs3769292; hg19: chr2-173726259;