rs3914129

Positions:

• chr7-103886418-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005045.4(RELN):​c.337+30657G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,056 control chromosomes in the GnomAD database, including 5,698 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 0.27 (5698 hom., cov: 32)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.854

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELN	NM_005045.4	c.337+30657G>A		intron_variant		ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.337+30657G>A		intron_variant			NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.337+30657G>A		intron_variant		5	NM_005045.4	ENSP00000392423	P5

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40339 AN: 151938 Hom.: 5701 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.265 AC: 40341 AN: 152056 Hom.: 5698 Cov.: 32 AF XY: 0.269 AC XY: 19983 AN XY: 74314

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.260

Alfa AF: 0.285 Hom.: 2913

Bravo AF: 0.264

Asia WGS AF: 0.350 AC: 1219 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	20
DANN	Benign	0.70

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: rs3914129; hg19: chr7-103526865;