rs16872603

chr7-103795160-A-G

Variant summary

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

The NM_005045.4(RELN):c.474-18533T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,214 control chromosomes in the GnomAD database, including 1,366 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 0.13 (1366 hom., cov: 33)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RELN	NM_005045.4	c.474-18533T>C		intron_variant		ENST00000428762.6
RELN	NM_173054.3	c.474-18533T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELN	ENST00000428762.6	c.474-18533T>C		intron_variant		5	NM_005045.4	P5

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19798 AN: 152096 Hom.: 1361 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.0908

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.130 AC: 19826 AN: 152214 Hom.: 1366 Cov.: 33 AF XY: 0.133 AC XY: 9892 AN XY: 74412

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0906

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.142

Alfa AF: 0.132 Hom.: 1384

Bravo AF: 0.118

Asia WGS AF: 0.158 AC: 550 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	7.5
Dann	Benign	0.69

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: rs16872603; hg19: chr7-103435607;