NM_006420.3:c.423+3A>G
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_006420.3(ARFGEF2):c.423+3A>G variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00364 in 1,614,124 control chromosomes in the GnomAD database, including 261 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_006420.3 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ARFGEF2 | NM_006420.3 | c.423+3A>G | splice_region_variant, intron_variant | Intron 4 of 38 | ENST00000371917.5 | NP_006411.2 | ||
ARFGEF2 | NM_001410846.1 | c.423+3A>G | splice_region_variant, intron_variant | Intron 4 of 38 | NP_001397775.1 | |||
ARFGEF2 | XM_047439832.1 | c.-142+3A>G | splice_region_variant, intron_variant | Intron 2 of 36 | XP_047295788.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00499 AC: 759AN: 152174Hom.: 27 Cov.: 31
GnomAD3 exomes AF: 0.0150 AC: 3780AN: 251400Hom.: 205 AF XY: 0.0109 AC XY: 1481AN XY: 135870
GnomAD4 exome AF: 0.00350 AC: 5111AN: 1461832Hom.: 234 Cov.: 32 AF XY: 0.00296 AC XY: 2156AN XY: 727226
GnomAD4 genome AF: 0.00500 AC: 761AN: 152292Hom.: 27 Cov.: 31 AF XY: 0.00542 AC XY: 404AN XY: 74478
ClinVar
Submissions by phenotype
not specified Benign:4
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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not provided Benign:2
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Periventricular heterotopia with microcephaly, autosomal recessive Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at