rs244739

Positions:

• chr5-131471181-A-C
• chr5-131471181-A-G

Variant summary

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

The NM_016340.6(RAPGEF6):​c.2239+1406T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,108 control chromosomes in the GnomAD database, including 4,130 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 0.22 (4130 hom., cov: 32)
• Consequence: RAPGEF6 NM_016340.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.773

Genes affected

RAPGEF6 (HGNC:20655): (Rap guanine nucleotide exchange factor 6) Enables several functions, including GTP-dependent protein binding activity; guanyl-nucleotide exchange factor activity; and phosphatidic acid binding activity. Involved in microvillus assembly; positive regulation of GTPase activity; and protein localization to plasma membrane. Located in several cellular components, including apical plasma membrane; centrosome; and endocytic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAPGEF6	NM_016340.6	c.2239+1406T>G		intron_variant		ENST00000509018.6	NP_057424.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAPGEF6	ENST00000509018.6	c.2239+1406T>G		intron_variant		1	NM_016340.6	ENSP00000421684	P4

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34077 AN: 151988 Hom.: 4120 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.224 AC: 34119 AN: 152108 Hom.: 4130 Cov.: 32 AF XY: 0.233 AC XY: 17340 AN XY: 74366

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.214

Alfa AF: 0.214 Hom.: 704

Bravo AF: 0.216

Asia WGS AF: 0.373 AC: 1299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.5
DANN	Benign	0.56

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: rs244739; hg19: chr5-130806874;