chr1-8355571-C-A

Variant names:

• chr1-8355571-C-A
• rs143882788
• NM_001042681.2:c.4515G>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001042681.2(RERE):​c.4515G>T​(p.Gly1505Gly) 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 Likely 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/Likely benign criteria provided, multiple submitters, no conflicts B:3
• 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

Our verdict: Benign. The variant received -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 [Likely_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 the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.
• BS2: High AC in GnomAd4 at 140 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RERE	NM_001042681.2	c.4515G>T	p.Gly1505Gly	synonymous_variant	Exon 22 of 23	ENST00000400908.7	NP_001036146.1
RERE	NM_012102.4	c.4515G>T	p.Gly1505Gly	synonymous_variant	Exon 23 of 24		NP_036234.3
RERE	NM_001042682.2	c.2853G>T	p.Gly951Gly	synonymous_variant	Exon 12 of 13		NP_001036147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RERE	ENST00000400908.7	c.4515G>T	p.Gly1505Gly	synonymous_variant	Exon 22 of 23	1	NM_001042681.2	ENSP00000383700.2

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

GnomAD2 exomes AF: 0.000869 AC: 200 AN: 230020 AF XY: 0.000919

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 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 AC: 5 AN: 33258

Gnomad4 AMR exome AF: 0.000706 AC: 31 AN: 43928

Gnomad4 ASJ exome AF: 0.00271 AC: 69 AN: 25504

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39396

Gnomad4 SAS exome AF: 0.000353 AC: 30 AN: 85080

Gnomad4 FIN exome AF: 0.000607 AC: 31 AN: 51082

Gnomad4 NFE exome AF: 0.000952 AC: 1050 AN: 1103258

Gnomad4 Remaining exome AF: 0.000955 AC: 57 AN: 59694

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 AC: 0.0000962279 AN: 0.0000962279

Gnomad4 AMR AF: 0.00176 AC: 0.00176424 AN: 0.00176424

Gnomad4 ASJ AF: 0.00403 AC: 0.00403458 AN: 0.00403458

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000414 AC: 0.00041425 AN: 0.00041425

Gnomad4 FIN AF: 0.000659 AC: 0.00065901 AN: 0.00065901

Gnomad4 NFE AF: 0.00121 AC: 0.00120588 AN: 0.00120588

Gnomad4 OTH AF: 0.00189 AC: 0.00189215 AN: 0.00189215

Alfa AF: 0.000879 Hom.: 0

Bravo AF: 0.00102

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RERE: BS1 -

Jan 07, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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
Mutation Taster		=99/1	polymorphism

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;