12-47748635-C-G

Position:

• chr12-47748635-C-G

Variant summary

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

The NM_001098531.4(RAPGEF3):​c.1155-93G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 1,239,608 control chromosomes in the GnomAD database, including 406,220 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 0.80 (49216 hom., cov: 32)
  • Exomes 𝑓: 0.81 (357004 hom.)
• Consequence: RAPGEF3 NM_001098531.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.717

Genes affected

RAPGEF3 (HGNC:16629): (Rap guanine nucleotide exchange factor 3) Enables guanyl-nucleotide exchange factor activity and protein domain specific binding activity. Involved in several processes, including positive regulation of protein modification process; regulation of actin cytoskeleton organization; and regulation of syncytium formation by plasma membrane fusion. Located in filopodium; lamellipodium; and microvillus. Colocalizes with cortical actin cytoskeleton and plasma membrane. Biomarker of congestive heart failure. [provided by Alliance of Genome Resources, Apr 2022]

RAPGEF3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAPGEF3	NM_001098531.4	c.1155-93G>C		intron_variant		ENST00000449771.7	NP_001092001.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAPGEF3	ENST00000449771.7	c.1155-93G>C		intron_variant		2	NM_001098531.4	ENSP00000395708.2
RAPGEF3	ENST00000389212.7	c.1155-93G>C		intron_variant		2		ENSP00000373864.3
RAPGEF3	ENST00000549151.5	c.1029-93G>C		intron_variant		5		ENSP00000448619.1
RAPGEF3	ENST00000548919.5	c.1029-93G>C		intron_variant		2		ENSP00000448480.1
RAPGEF3	ENST00000395358.7	c.1155-93G>C		intron_variant		2		ENSP00000378764.3
RAPGEF3	ENST00000495465.6	n.*272-93G>C		intron_variant		3		ENSP00000449818.1
RAPGEF3	ENST00000547856.5	n.*463-93G>C		intron_variant		2		ENSP00000449905.1

Frequencies

GnomAD3 genomes AF: 0.803 AC: 122027 AN: 152026 Hom.: 49162 Cov.: 32

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.941

Gnomad SAS AF: 0.724

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.808

GnomAD4 exome AF: 0.808 AC: 879053 AN: 1087464 Hom.: 357004 Cov.: 14 AF XY: 0.804 AC XY: 442169 AN XY: 550194

Gnomad4 AFR exome AF: 0.773

Gnomad4 AMR exome AF: 0.876

Gnomad4 ASJ exome AF: 0.828

Gnomad4 EAS exome AF: 0.918

Gnomad4 SAS exome AF: 0.698

Gnomad4 FIN exome AF: 0.733

Gnomad4 NFE exome AF: 0.816

Gnomad4 OTH exome AF: 0.806

GnomAD4 genome AF: 0.803 AC: 122143 AN: 152144 Hom.: 49216 Cov.: 32 AF XY: 0.800 AC XY: 59464 AN XY: 74376

Gnomad4 AFR AF: 0.775

Gnomad4 AMR AF: 0.857

Gnomad4 ASJ AF: 0.826

Gnomad4 EAS AF: 0.941

Gnomad4 SAS AF: 0.724

Gnomad4 FIN AF: 0.719

Gnomad4 NFE AF: 0.816

Gnomad4 OTH AF: 0.811

Alfa AF: 0.772 Hom.: 2355

Bravo AF: 0.816

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.20
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs757281; hg19: chr12-48142418;