rs10248053

chr7-103524206-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.7350-675A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 152,004 control chromosomes in the GnomAD database, including 10,895 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 0.32 (10895 hom., cov: 32)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.475

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RELN	NM_005045.4	c.7350-675A>G		intron_variant		ENST00000428762.6
RELN	NM_173054.3	c.7350-675A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELN	ENST00000428762.6	c.7350-675A>G		intron_variant		5	NM_005045.4	P5

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49137 AN: 151886 Hom.: 10850 Cov.: 32

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.324 AC: 49260 AN: 152004 Hom.: 10895 Cov.: 32 AF XY: 0.326 AC XY: 24232 AN XY: 74302

Gnomad4 AFR AF: 0.604

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.541

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.313

Alfa AF: 0.242 Hom.: 1670

Bravo AF: 0.342

Asia WGS AF: 0.542 AC: 1883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.76
Dann	Benign	0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10248053; hg19: chr7-103164653;