5-131548303-T-G

Variant names:

• chr5-131548303-T-G
• rs17671387
• NM_016340.6:c.352-113A>C

Variant summary

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

The NM_016340.6(RAPGEF6):​c.352-113A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0625 in 1,055,606 control chromosomes in the GnomAD database, including 2,503 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 0.051 (269 hom., cov: 31)
  • Exomes 𝑓: 0.064 (2234 hom.)
• Consequence: RAPGEF6 NM_016340.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAPGEF6	NM_016340.6	c.352-113A>C		intron_variant	Intron 5 of 27	ENST00000509018.6	NP_057424.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAPGEF6	ENST00000509018.6	c.352-113A>C		intron_variant	Intron 5 of 27	1	NM_016340.6	ENSP00000421684.1
ENSG00000273217	ENST00000514667.1	c.502-113A>C		intron_variant	Intron 6 of 28	2		ENSP00000426948.1

Frequencies

GnomAD3 genomes AF: 0.0513 AC: 7804 AN: 152158 Hom.: 268 Cov.: 31

Gnomad AFR AF: 0.0132

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0332

Gnomad ASJ AF: 0.0920

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0470

Gnomad FIN AF: 0.0739

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0771

Gnomad OTH AF: 0.0469

GnomAD4 exome AF: 0.0644 AC: 58199 AN: 903330 Hom.: 2234 AF XY: 0.0643 AC XY: 29481 AN XY: 458338

Gnomad4 AFR exome AF: 0.0108

Gnomad4 AMR exome AF: 0.0249

Gnomad4 ASJ exome AF: 0.0974

Gnomad4 EAS exome AF: 0.000484

Gnomad4 SAS exome AF: 0.0430

Gnomad4 FIN exome AF: 0.0724

Gnomad4 NFE exome AF: 0.0720

Gnomad4 OTH exome AF: 0.0585

GnomAD4 genome AF: 0.0513 AC: 7806 AN: 152276 Hom.: 269 Cov.: 31 AF XY: 0.0505 AC XY: 3763 AN XY: 74476

Gnomad4 AFR AF: 0.0132

Gnomad4 AMR AF: 0.0331

Gnomad4 ASJ AF: 0.0920

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0477

Gnomad4 FIN AF: 0.0739

Gnomad4 NFE AF: 0.0770

Gnomad4 OTH AF: 0.0464

Alfa AF: 0.0628 Hom.: 204

Bravo AF: 0.0457

Asia WGS AF: 0.0220 AC: 77 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	8.9
DANN	Benign	0.66

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: rs17671387; hg19: chr5-130883996;