Variant 5-131430849-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00100

Variant links:

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]

RAPGEF6 links:

ENSG00000273217 (HGNC:):

ENSG00000273217 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
RAPGEF6	NM_016340.6 linkuse as main transcript	c.4465+10G>T	intron_variant	ENST00000509018.6	NP_057424.3	Q8TEU7-1
RAPGEF6	NM_001164386.2 linkuse as main transcript	c.4489+10G>T	intron_variant		NP_001157858.1	Q8TEU7-4B2RTU6
RAPGEF6	NM_001164387.2 linkuse as main transcript	c.4504+10G>T	intron_variant		NP_001157859.1	Q8TEU7-3
RAPGEF6	NM_001164388.2 linkuse as main transcript	c.4489+10G>T	intron_variant		NP_001157860.1	Q8TEU7-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAPGEF6	ENST00000509018.6 linkuse as main transcript	c.4465+10G>T		intron_variant		1	NM_016340.6	ENSP00000421684.1		Q8TEU7-1
ENSG00000273217	ENST00000514667.1 linkuse as main transcript	c.4615+10G>T		intron_variant		2		ENSP00000426948.1		E9PCH4

Frequencies

GnomAD3 genomes

AF:

0.0286

AC:

4356

AN:

152162

Hom.:

230

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00754

AC:

1707

AN:

226410

Hom.:

AF XY:

0.00568

AC XY:

695

AN XY:

122300

show subpopulations

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 SAS exome

AF:

0.0000395

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.:

AF XY:

0.00234

AC XY:

1664

AN XY:

712256

show subpopulations

Gnomad4 AFR exome

AF:

0.101

Gnomad4 AMR exome

AF:

0.00514

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000982

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000999

Gnomad4 OTH exome

AF:

0.00548

GnomAD4 genome

AF:

0.0286

AC:

4358

AN:

152280

Hom.:

230

Cov.:

AF XY:

0.0278

AC XY:

2067

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0993

Gnomad4 AMR

AF:

0.0108

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.0208

Alfa

AF:

0.0218

Hom.:

Bravo

AF:

0.0333

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

6.2

DANN

Benign

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over