NM_016340.6:c.495+1759C>A

Variant names:

• chr5-131546288-G-T
• rs7714362
• NM_016340.6:c.495+1759C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016340.6(RAPGEF6):​c.495+1759C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,078 control chromosomes in the GnomAD database, including 3,364 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 0.13 (3364 hom., cov: 32)
• Consequence: RAPGEF6 NM_016340.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016340.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAPGEF6	NM_016340.6	MANE Select	c.495+1759C>A		intron	N/A	NP_057424.3
	RAPGEF6	NM_001164386.2		c.495+1759C>A		intron	N/A	NP_001157858.1
	RAPGEF6	NM_001164387.2		c.495+1759C>A		intron	N/A	NP_001157859.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAPGEF6	ENST00000509018.6	TSL:1 MANE Select	c.495+1759C>A		intron	N/A	ENSP00000421684.1
	ENSG00000273217	ENST00000514667.1	TSL:2	c.645+1759C>A		intron	N/A	ENSP00000426948.1
	RAPGEF6	ENST00000296859.10	TSL:1	c.495+1759C>A		intron	N/A	ENSP00000296859.6

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19039 AN: 151960 Hom.: 3348 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0557

Gnomad ASJ AF: 0.0580

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0133

Gnomad FIN AF: 0.00359

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.0181

Gnomad OTH AF: 0.0944

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

GnomAD4 genome AF: 0.126 AC: 19089 AN: 152078 Hom.: 3364 Cov.: 32 AF XY: 0.121 AC XY: 9012 AN XY: 74378

African (AFR) AF: 0.398 AC: 16478 AN: 41420

American (AMR) AF: 0.0557 AC: 851 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0580 AC: 201 AN: 3464

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0133 AC: 64 AN: 4824

European-Finnish (FIN) AF: 0.00359 AC: 38 AN: 10590

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 292

European-Non Finnish (NFE) AF: 0.0181 AC: 1229 AN: 68000

Other (OTH) AF: 0.0935 AC: 197 AN: 2108

Alfa AF: 0.0932 Hom.: 321

Bravo AF: 0.143

Asia WGS AF: 0.0300 AC: 106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.79
DANN	Benign	0.28
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7714362; hg19: chr5-130881981;