rs73786670

Variant names:

• chr5-131430849-C-A
• rs73786670
• NM_016340.6:c.4465+10G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-131430849-C-A
• chr5-131430849-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016340.6(RAPGEF6):​c.4465+10G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00521 in 1,586,990 control chromosomes in the GnomAD database, including 419 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (230 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (189 hom.)
• Consequence: RAPGEF6 NM_016340.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00100
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 5-131430849-C-A is Benign according to our data. Variant chr5-131430849-C-A is described in ClinVar as Benign. ClinVar VariationId is 776064.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0968 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAPGEF6	NM_016340.6	MANE Select	c.4465+10G>T		intron	N/A	NP_057424.3	Q8TEU7-1
	RAPGEF6	NM_001164386.2		c.4489+10G>T		intron	N/A	NP_001157858.1	Q8TEU7-4
	RAPGEF6	NM_001164387.2		c.4504+10G>T		intron	N/A	NP_001157859.1	Q8TEU7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAPGEF6	ENST00000509018.6	TSL:1 MANE Select	c.4465+10G>T		intron	N/A	ENSP00000421684.1	Q8TEU7-1
	ENSG00000273217	ENST00000514667.1	TSL:2	c.4615+10G>T		intron	N/A	ENSP00000426948.1	E9PCH4
	RAPGEF6	ENST00000296859.10	TSL:1	c.4489+10G>T		intron	N/A	ENSP00000296859.6	Q8TEU7-4

Frequencies

GnomAD3 genomes AF: 0.0286 AC: 4356 AN: 152162 Hom.: 230 Cov.: 32

Gnomad AFR AF: 0.0996

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0108

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0211

GnomAD2 exomes AF: 0.00754 AC: 1707 AN: 226410 AF XY: 0.00568

Gnomad AFR exome AF: 0.0982

Gnomad AMR exome AF: 0.00449

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000181

Gnomad OTH exome AF: 0.00427

GnomAD4 exome AF: 0.00273 AC: 3914 AN: 1434710 Hom.: 189 Cov.: 29 AF XY: 0.00234 AC XY: 1664 AN XY: 712256

African (AFR) AF: 0.101 AC: 3234 AN: 32036

American (AMR) AF: 0.00514 AC: 201 AN: 39102

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39564

South Asian (SAS) AF: 0.0000982 AC: 8 AN: 81498

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52478

Middle Eastern (MID) AF: 0.00662 AC: 37 AN: 5590

European-Non Finnish (NFE) AF: 0.0000999 AC: 110 AN: 1101258

Other (OTH) AF: 0.00548 AC: 324 AN: 59108

GnomAD4 genome AF: 0.0286 AC: 4358 AN: 152280 Hom.: 230 Cov.: 32 AF XY: 0.0278 AC XY: 2067 AN XY: 74464

African (AFR) AF: 0.0993 AC: 4126 AN: 41532

American (AMR) AF: 0.0108 AC: 165 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68024

Other (OTH) AF: 0.0208 AC: 44 AN: 2112

Alfa AF: 0.0243 Hom.: 62

Bravo AF: 0.0333

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.2
DANN	Benign	0.74
PhyloP100		-0.0010
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: rs73786670; hg19: chr5-130766542;