rs12536007

Positions:

• chr7-103841241-C-G
• chr7-103841241-C-T

Variant summary

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

The NM_005045.4(RELN):​c.338-7569G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0591 in 152,202 control chromosomes in the GnomAD database, including 502 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 0.059 (502 hom., cov: 32)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELN	NM_005045.4	c.338-7569G>C		intron_variant		ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.338-7569G>C		intron_variant			NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.338-7569G>C		intron_variant		5	NM_005045.4	ENSP00000392423	P5

Frequencies

GnomAD3 genomes AF: 0.0591 AC: 8989 AN: 152084 Hom.: 506 Cov.: 32

Gnomad AFR AF: 0.0162

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.0318

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0554

Gnomad OTH AF: 0.0650

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

GnomAD4 genome AF: 0.0591 AC: 8991 AN: 152202 Hom.: 502 Cov.: 32 AF XY: 0.0627 AC XY: 4663 AN XY: 74412

Gnomad4 AFR AF: 0.0161

Gnomad4 AMR AF: 0.100

Gnomad4 ASJ AF: 0.0340

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.0318

Gnomad4 NFE AF: 0.0554

Gnomad4 OTH AF: 0.0658

Alfa AF: 0.0255 Hom.: 11

Bravo AF: 0.0603

Asia WGS AF: 0.204 AC: 712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.92
DANN	Benign	0.47

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: rs12536007; hg19: chr7-103481688;