5-131460875-A-T

Position:

• chr5-131460875-A-T

Variant summary

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

The NM_016340.6(RAPGEF6):​c.2864+830T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,090 control chromosomes in the GnomAD database, including 3,999 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 (3999 hom., cov: 32)
• Consequence: RAPGEF6 NM_016340.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.377

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]

ENSG00000273217 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAPGEF6	NM_016340.6	c.2864+830T>A		intron_variant		ENST00000509018.6	NP_057424.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAPGEF6	ENST00000509018.6	c.2864+830T>A		intron_variant		1	NM_016340.6	ENSP00000421684.1
ENSG00000273217	ENST00000514667.1	c.3014+830T>A		intron_variant		2		ENSP00000426948.1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33309 AN: 151972 Hom.: 3991 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.219 AC: 33346 AN: 152090 Hom.: 3999 Cov.: 32 AF XY: 0.228 AC XY: 16953 AN XY: 74342

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.209

Alfa AF: 0.219 Hom.: 459

Bravo AF: 0.211

Asia WGS AF: 0.370 AC: 1288 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.46

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: rs739952; hg19: chr5-130796568;