7-103803583-T-C

Position:

• chr7-103803583-T-C

Variant summary

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

The NM_005045.4(RELN):​c.474-26956A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 151,952 control chromosomes in the GnomAD database, including 5,361 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 0.26 (5361 hom., cov: 32)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.932

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]

RELN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELN	NM_005045.4	c.474-26956A>G		intron_variant		ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.474-26956A>G		intron_variant			NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.474-26956A>G		intron_variant		5	NM_005045.4	ENSP00000392423.1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40029 AN: 151834 Hom.: 5361 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.264 AC: 40055 AN: 151952 Hom.: 5361 Cov.: 32 AF XY: 0.261 AC XY: 19374 AN XY: 74278

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.267

Alfa AF: 0.253 Hom.: 2303

Bravo AF: 0.275

Asia WGS AF: 0.284 AC: 988 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.94
DANN	Benign	0.68

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: rs1963647; hg19: chr7-103444030;