rs1422871

Positions:

• chr5-131606788-G-A
• chr5-131606788-G-C

Variant summary

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

The NM_016340.6(RAPGEF6):​c.70-2095C>T 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 152,116 control chromosomes in the GnomAD database, including 46,622 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 (46622 hom., cov: 32)
• Consequence: RAPGEF6 NM_016340.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.173

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAPGEF6	NM_016340.6	c.70-2095C>T		intron_variant		ENST00000509018.6	NP_057424.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAPGEF6	ENST00000509018.6	c.70-2095C>T		intron_variant		1	NM_016340.6	ENSP00000421684.1
ENSG00000273217	ENST00000514667.1	c.220-2095C>T		intron_variant		2		ENSP00000426948.1

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118518 AN: 151998 Hom.: 46591 Cov.: 32

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.733

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.801

Gnomad OTH AF: 0.791

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

GnomAD4 genome AF: 0.780 AC: 118602 AN: 152116 Hom.: 46622 Cov.: 32 AF XY: 0.771 AC XY: 57314 AN XY: 74352

Gnomad4 AFR AF: 0.836

Gnomad4 AMR AF: 0.752

Gnomad4 ASJ AF: 0.723

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.752

Gnomad4 FIN AF: 0.639

Gnomad4 NFE AF: 0.801

Gnomad4 OTH AF: 0.791

Alfa AF: 0.768 Hom.: 6953

Bravo AF: 0.788

Asia WGS AF: 0.617 AC: 2146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.39

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: rs1422871; hg19: chr5-130942481;