5-131557048-A-G

Position:

• chr5-131557048-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.351+4930T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,108 control chromosomes in the GnomAD database, including 46,565 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 0.78 (46565 hom., cov: 31)
• Consequence: RAPGEF6 NM_016340.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.765

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAPGEF6	NM_016340.6	c.351+4930T>C		intron_variant		ENST00000509018.6	NP_057424.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAPGEF6	ENST00000509018.6	c.351+4930T>C		intron_variant		1	NM_016340.6	ENSP00000421684	P4

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118499 AN: 151988 Hom.: 46535 Cov.: 31

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.790

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

GnomAD4 genome AF: 0.780 AC: 118581 AN: 152108 Hom.: 46565 Cov.: 31 AF XY: 0.771 AC XY: 57284 AN XY: 74334

Gnomad4 AFR AF: 0.834

Gnomad4 AMR AF: 0.751

Gnomad4 ASJ AF: 0.720

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.743

Gnomad4 FIN AF: 0.639

Gnomad4 NFE AF: 0.802

Gnomad4 OTH AF: 0.790

Alfa AF: 0.785 Hom.: 6827

Bravo AF: 0.789

Asia WGS AF: 0.622 AC: 2163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.45
DANN	Benign	0.20

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: rs6873582; hg19: chr5-130892741;