rs39346

Positions:

• chr7-103825821-G-A

Variant summary

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

The NM_005045.4(RELN):​c.473+7716C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 151,954 control chromosomes in the GnomAD database, including 2,169 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 0.16 (2169 hom., cov: 32)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227

Genes affected

RELN (HGNC:9957): (reelin) This gene encodes a large secreted extracellular matrix protein thought to control cell-cell interactions critical for cell positioning and neuronal migration during brain development. This protein may be involved in schizophrenia, autism, bipolar disorder, major depression and in migration defects associated with temporal lobe epilepsy. Mutations of this gene are associated with autosomal recessive lissencephaly with cerebellar hypoplasia. Two transcript variants encoding distinct isoforms have been identified for this gene. Other transcript variants have been described but their full length nature has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELN	NM_005045.4	c.473+7716C>T		intron_variant		ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.473+7716C>T		intron_variant			NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.473+7716C>T		intron_variant		5	NM_005045.4	ENSP00000392423	P5

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24701 AN: 151836 Hom.: 2166 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0955

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.163 AC: 24719 AN: 151954 Hom.: 2169 Cov.: 32 AF XY: 0.161 AC XY: 11991 AN XY: 74258

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.0957

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.136

Alfa AF: 0.175 Hom.: 2382

Bravo AF: 0.163

Asia WGS AF: 0.106 AC: 368 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.1
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs39346; hg19: chr7-103466268;