1-8355571-C-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001042681.2(RERE):c.4515G>T(p.Gly1505=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000887 in 1,599,088 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00092 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00088 (1 hom.)
• Consequence: RERE NM_001042681.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.332

Genes affected

RERE (HGNC:9965): (arginine-glutamic acid dipeptide repeats) This gene encodes a member of the atrophin family of arginine-glutamic acid (RE) dipeptide repeat-containing proteins. The encoded protein co-localizes with a transcription factor in the nucleus, and its overexpression triggers apoptosis. A similar protein in mouse associates with histone deacetylase and is thought to function as a transcriptional co-repressor during embryonic development. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 1-8355571-C-A is Benign according to our data. Variant chr1-8355571-C-A is described in ClinVar as [Benign]. Clinvar id is 1600804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000919 (140/152296) while in subpopulation AMR AF= 0.00176 (27/15304). AF 95% confidence interval is 0.00124. There are 1 homozygotes in gnomad4. There are 71 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 140 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RERE	NM_001042681.2	c.4515G>T	p.Gly1505=	synonymous_variant	22/23	ENST00000400908.7
RERE	NM_012102.4	c.4515G>T	p.Gly1505=	synonymous_variant	23/24
RERE	NM_001042682.2	c.2853G>T	p.Gly951=	synonymous_variant	12/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RERE	ENST00000400908.7	c.4515G>T	p.Gly1505=	synonymous_variant	22/23	1	NM_001042681.2	P1

Frequencies

GnomAD3 genomes AF: 0.000920 AC: 140 AN: 152178 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00121

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000869 AC: 200 AN: 230020 Hom.: 0 AF XY: 0.000919 AC XY: 116 AN XY: 126186

Gnomad AFR exome AF: 0.0000691

Gnomad AMR exome AF: 0.000567

Gnomad ASJ exome AF: 0.00324

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000446

Gnomad FIN exome AF: 0.000600

Gnomad NFE exome AF: 0.00121

Gnomad OTH exome AF: 0.000891

GnomAD4 exome AF: 0.000884 AC: 1279 AN: 1446792 Hom.: 1 Cov.: 32 AF XY: 0.000932 AC XY: 669 AN XY: 717696

Gnomad4 AFR exome AF: 0.000150

Gnomad4 AMR exome AF: 0.000706

Gnomad4 ASJ exome AF: 0.00271

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000353

Gnomad4 FIN exome AF: 0.000607

Gnomad4 NFE exome AF: 0.000952

Gnomad4 OTH exome AF: 0.000955

GnomAD4 genome AF: 0.000919 AC: 140 AN: 152296 Hom.: 1 Cov.: 33 AF XY: 0.000953 AC XY: 71 AN XY: 74470

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.00176

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00121

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000879 Hom.: 0

Bravo AF: 0.00102

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	RERE: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	14
Dann	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.24		Position offset: -23

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs143882788; hg19: chr1-8415631;