rs3763188

Variant names:

• chr6-138925939-T-C
• rs3763188
• NM_001286611.2:c.1338+462A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• neurodegeneration with brain iron accumulation 7

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286611.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REPS1	NM_001286611.2	MANE Select	c.1338+462A>G		intron	N/A	NP_001273540.1
	REPS1	NM_031922.5		c.1338+462A>G		intron	N/A	NP_114128.3
	REPS1	NM_001128617.3		c.1257+4038A>G		intron	N/A	NP_001122089.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REPS1	ENST00000450536.7	TSL:1 MANE Select	c.1338+462A>G		intron	N/A	ENSP00000392065.2
	REPS1	ENST00000258062.9	TSL:1	c.1338+462A>G		intron	N/A	ENSP00000258062.5
	REPS1	ENST00000409812.6	TSL:1	c.1257+4038A>G		intron	N/A	ENSP00000386699.2

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

African (AFR) AF: 0.0772 AC: 3205 AN: 41532

American (AMR) AF: 0.130 AC: 1987 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 704 AN: 3470

East Asian (EAS) AF: 0.296 AC: 1530 AN: 5168

South Asian (SAS) AF: 0.351 AC: 1692 AN: 4826

European-Finnish (FIN) AF: 0.0910 AC: 963 AN: 10588

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10908 AN: 68014

Other (OTH) AF: 0.142 AC: 301 AN: 2114

Alfa AF: 0.161 Hom.: 9095

Bravo AF: 0.137

Asia WGS AF: 0.261 AC: 908 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Benign	0.75
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3763188; hg19: chr6-139247076;