rs3763188

chr6-138925939-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286611.2(REPS1):c.1338+462A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,210 control chromosomes in the GnomAD database, including 1,816 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1816 hom., cov: 32)
• Consequence: REPS1 NM_001286611.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REPS1	NM_001286611.2	c.1338+462A>G		intron_variant		ENST00000450536.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REPS1	ENST00000450536.7	c.1338+462A>G		intron_variant		1	NM_001286611.2	P4

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21583 AN: 152092 Hom.: 1817 Cov.: 32

Gnomad AFR AF: 0.0773

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.0910

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.145

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.142 AC: 21570 AN: 152210 Hom.: 1816 Cov.: 32 AF XY: 0.142 AC XY: 10573 AN XY: 74414

Gnomad4 AFR AF: 0.0772

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.0910

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.142

Alfa AF: 0.166 Hom.: 4524

Bravo AF: 0.137

Asia WGS AF: 0.261 AC: 908 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	14
Dann	Benign	0.75

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

Other links and lift over

dbSNP: rs3763188; hg19: chr6-139247076;