rs301819

Variant names:

• chr1-8441726-A-G
• rs301819
• NM_001042681.2:c.1204-18919T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-8441726-A-G
• chr1-8441726-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042681.2(RERE):​c.1204-18919T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 152,002 control chromosomes in the GnomAD database, including 29,734 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 0.62 (29734 hom., cov: 32)
• Consequence: RERE NM_001042681.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209
• Publications: 27 publications found

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]

RERE Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder with or without congenital anomalies

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• neurodevelopmental disorder with or without anomalies of the brain, eye, or heart

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RERE	NM_001042681.2	c.1204-18919T>C		intron_variant	Intron 11 of 22	ENST00000400908.7	NP_001036146.1
RERE	NM_012102.4	c.1204-18919T>C		intron_variant	Intron 12 of 23		NP_036234.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RERE	ENST00000400908.7	c.1204-18919T>C		intron_variant	Intron 11 of 22	1	NM_001042681.2	ENSP00000383700.2

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93940 AN: 151884 Hom.: 29702 Cov.: 32

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.619 AC: 94032 AN: 152002 Hom.: 29734 Cov.: 32 AF XY: 0.622 AC XY: 46241 AN XY: 74284

African (AFR) AF: 0.694 AC: 28766 AN: 41462

American (AMR) AF: 0.619 AC: 9448 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1414 AN: 3468

East Asian (EAS) AF: 0.838 AC: 4336 AN: 5174

South Asian (SAS) AF: 0.490 AC: 2359 AN: 4814

European-Finnish (FIN) AF: 0.675 AC: 7125 AN: 10560

Middle Eastern (MID) AF: 0.329 AC: 96 AN: 292

European-Non Finnish (NFE) AF: 0.571 AC: 38768 AN: 67950

Other (OTH) AF: 0.557 AC: 1176 AN: 2112

Alfa AF: 0.576 Hom.: 25692

Bravo AF: 0.620

Asia WGS AF: 0.656 AC: 2280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.8
DANN	Benign	0.45
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs301819; hg19: chr1-8501786; COSMIC: COSV61936702;