Variant 6-138905135-GA-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_001286611.2(REPS1):c.2323-4del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00324 in 1,597,242 control chromosomes in the GnomAD database, including 18 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 17 hom. )

Consequence

REPS1
NM_001286611.2 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.234

Variant links:

Genes affected

REPS1 (HGNC:15578): (RALBP1 associated Eps domain containing 1) This gene encodes a signaling adaptor protein with two EH domains that interacts with proteins that participate in signaling, endocytosis and cytoskeletal changes. The encoded protein has been found in association with intersectin 1 and Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1 when intersectin 1 was isolated from clathrin-coated pits. The encoded protein has also been shown to interact with amphiphysin, a cytoplasmic protein at the surface of synaptic vesicles. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

REPS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

Variant 6-138905135-GA-G is Benign according to our data. Variant chr6-138905135-GA-G is described in ClinVar as [Likely_benign]. Clinvar id is 1599842.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-138905135-GA-G is described in Lovd as [Benign].

BS2

High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REPS1	NM_001286611.2 linkuse as main transcript	c.2323-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000450536.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REPS1	ENST00000450536.7 linkuse as main transcript	c.2323-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001286611.2	P4	Q96D71-1

Frequencies

GnomAD3 genomes

AF:

0.00222

AC:

338

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00363

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00291

AC:

728

AN:

250520

Hom.:

AF XY:

0.00309

AC XY:

418

AN XY:

135418

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00122

Gnomad ASJ exome

AF:

0.00457

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00473

Gnomad FIN exome

AF:

0.00245

Gnomad NFE exome

AF:

0.00371

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00334

AC:

4830

AN:

1445008

Hom.:

Cov.:

AF XY:

0.00341

AC XY:

2456

AN XY:

719888

show subpopulations

Gnomad4 AFR exome

AF:

0.000514

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.00431

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00455

Gnomad4 FIN exome

AF:

0.00266

Gnomad4 NFE exome

AF:

0.00356

Gnomad4 OTH exome

AF:

0.00313

GnomAD4 genome

AF:

0.00222

AC:

338

AN:

152234

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

141

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00559

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00363

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00262

Hom.:

Bravo

AF:

0.00201

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00421

EpiControl

AF:

0.00386

ClinVar

Significance: Benign/Likely 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	Dec 11, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	REPS1: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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