Variant 12-47741043-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001098531.4(RAPGEF3):c.1924-3C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00622 in 1,612,162 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0049 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0064 ( 54 hom. )

Consequence

RAPGEF3
NM_001098531.4 splice_region, intron

Scores

Splicing: ADA: 0.005378

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.84

Variant links:

Genes affected

RAPGEF3 (HGNC:16629): (Rap guanine nucleotide exchange factor 3) Enables guanyl-nucleotide exchange factor activity and protein domain specific binding activity. Involved in several processes, including positive regulation of protein modification process; regulation of actin cytoskeleton organization; and regulation of syncytium formation by plasma membrane fusion. Located in filopodium; lamellipodium; and microvillus. Colocalizes with cortical actin cytoskeleton and plasma membrane. Biomarker of congestive heart failure. [provided by Alliance of Genome Resources, Apr 2022]

RAPGEF3 links:

RPAP3-DT (HGNC:):

RPAP3-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 12-47741043-G-A is Benign according to our data. Variant chr12-47741043-G-A is described in ClinVar as [Benign]. Clinvar id is 790861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAPGEF3	NM_001098531.4 linkuse as main transcript	c.1924-3C>T		splice_region_variant, intron_variant		ENST00000449771.7	NP_001092001.2	Q99777

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
RAPGEF3	ENST00000449771.7 linkuse as main transcript	c.1924-3C>T	splice_region_variant, intron_variant	2	NM_001098531.4	ENSP00000395708.2	O95398-1
RAPGEF3	ENST00000389212.7 linkuse as main transcript	c.1924-3C>T	splice_region_variant, intron_variant	2		ENSP00000373864.3	O95398-1
RAPGEF3	ENST00000549151.5 linkuse as main transcript	c.1798-3C>T	splice_region_variant, intron_variant	5		ENSP00000448619.1	O95398-3
RAPGEF3	ENST00000548919.5 linkuse as main transcript	c.1651-3C>T	splice_region_variant, intron_variant	2		ENSP00000448480.1	F8VRX1
RAPGEF3	ENST00000547856.5 linkuse as main transcript	n.*1232-3C>T	splice_region_variant, intron_variant	2		ENSP00000449905.1	F8VVJ6

Frequencies

GnomAD3 genomes

AF:

0.00494

AC:

752

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0172

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00692

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00596

AC:

1440

AN:

241720

Hom.:

AF XY:

0.00650

AC XY:

855

AN XY:

131494

show subpopulations

Gnomad AFR exome

AF:

0.000461

Gnomad AMR exome

AF:

0.00311

Gnomad ASJ exome

AF:

0.00334

Gnomad EAS exome

AF:

0.0000551

Gnomad SAS exome

AF:

0.0142

Gnomad FIN exome

AF:

0.00324

Gnomad NFE exome

AF:

0.00707

Gnomad OTH exome

AF:

0.00624

GnomAD4 exome

AF:

0.00635

AC:

9275

AN:

1459820

Hom.:

Cov.:

AF XY:

0.00665

AC XY:

4825

AN XY:

726090

show subpopulations

Gnomad4 AFR exome

AF:

0.000896

Gnomad4 AMR exome

AF:

0.00337

Gnomad4 ASJ exome

AF:

0.00372

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0149

Gnomad4 FIN exome

AF:

0.00434

Gnomad4 NFE exome

AF:

0.00632

Gnomad4 OTH exome

AF:

0.00614

GnomAD4 genome

AF:

0.00494

AC:

752

AN:

152342

Hom.:

Cov.:

AF XY:

0.00510

AC XY:

380

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00399

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0174

Gnomad4 FIN

AF:

0.00405

Gnomad4 NFE

AF:

0.00692

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00555

Hom.:

Bravo

AF:

0.00452

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0054

dbscSNV1_RF

Benign

0.12

SpliceAI score (max)

0.16

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