Variant chr5-131430929-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_016340.6(RAPGEF6):c.4395C>A(p.Gly1465Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00786 in 1,613,936 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0051 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 70 hom. )

Consequence

RAPGEF6
NM_016340.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.33

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 5-131430929-G-T is Benign according to our data. Variant chr5-131430929-G-T is described in ClinVar as [Benign]. Clinvar id is 718742.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=3.33 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAPGEF6	NM_016340.6 linkuse as main transcript	c.4395C>A	p.Gly1465Gly	synonymous_variant	26/28	ENST00000509018.6	NP_057424.3	Q8TEU7-1
RAPGEF6	NM_001164386.2 linkuse as main transcript	c.4419C>A	p.Gly1473Gly	synonymous_variant	27/29		NP_001157858.1	Q8TEU7-4B2RTU6
RAPGEF6	NM_001164387.2 linkuse as main transcript	c.4434C>A	p.Gly1478Gly	synonymous_variant	28/29		NP_001157859.1	Q8TEU7-3
RAPGEF6	NM_001164388.2 linkuse as main transcript	c.4419C>A	p.Gly1473Gly	synonymous_variant	27/28		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.4395C>A	p.Gly1465Gly	synonymous_variant	26/28	1	NM_016340.6	ENSP00000421684.1		Q8TEU7-1
ENSG00000273217	ENST00000514667.1 linkuse as main transcript	c.4545C>A	p.Gly1515Gly	synonymous_variant	27/29	2		ENSP00000426948.1		E9PCH4

Frequencies

GnomAD3 genomes

AF:

0.00513

AC:

781

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00801

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00539

AC:

1354

AN:

251114

Hom.:

AF XY:

0.00595

AC XY:

807

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00238

Gnomad ASJ exome

AF:

0.00428

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0108

Gnomad FIN exome

AF:

0.00236

Gnomad NFE exome

AF:

0.00698

Gnomad OTH exome

AF:

0.00588

GnomAD4 exome

AF:

0.00815

AC:

11911

AN:

1461630

Hom.:

Cov.:

AF XY:

0.00826

AC XY:

6006

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.00137

Gnomad4 AMR exome

AF:

0.00253

Gnomad4 ASJ exome

AF:

0.00429

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0115

Gnomad4 FIN exome

AF:

0.00286

Gnomad4 NFE exome

AF:

0.00906

Gnomad4 OTH exome

AF:

0.00674

GnomAD4 genome

AF:

0.00513

AC:

781

AN:

152306

Hom.:

Cov.:

AF XY:

0.00509

AC XY:

379

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00192

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0122

Gnomad4 FIN

AF:

0.00226

Gnomad4 NFE

AF:

0.00801

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00665

Hom.:

Bravo

AF:

0.00481

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.00682

EpiControl

AF:

0.00711

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

Jul 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.4

DANN

Benign

0.64

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