chr2-172795130-A-G

Position:

• chr2-172795130-A-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_007023.4(RAPGEF4):​c.171A>G​(p.Leu57Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAPGEF4 NM_007023.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.604

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 Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 2-172795130-A-G is Benign according to our data. Variant chr2-172795130-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 726968.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.604 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAPGEF4	NM_007023.4	c.171A>G	p.Leu57Leu	synonymous_variant	2/31	ENST00000397081.8	NP_008954.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAPGEF4	ENST00000397081.8	c.171A>G	p.Leu57Leu	synonymous_variant	2/31	1	NM_007023.4	ENSP00000380271.3
RAPGEF4	ENST00000409036.5	c.171A>G	p.Leu57Leu	synonymous_variant	2/28	5		ENSP00000387104.1
RAPGEF4	ENST00000464976.1	n.392A>G		non_coding_transcript_exon_variant	2/4	1
RAPGEF4	ENST00000484331.5	n.238A>G		non_coding_transcript_exon_variant	2/5	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.8
DANN	Benign	0.70

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: rs1574860852; hg19: chr2-173659858; COSMIC: COSV51383399;