7-103813122-T-C

Position:

• chr7-103813122-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.473+20415A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,188 control chromosomes in the GnomAD database, including 3,576 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 0.20 (3576 hom., cov: 32)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

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 (AFR) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELN	NM_005045.4	c.473+20415A>G		intron_variant		ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.473+20415A>G		intron_variant			NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.473+20415A>G		intron_variant		5	NM_005045.4	ENSP00000392423	P5

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31078 AN: 152070 Hom.: 3580 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0531

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.204 AC: 31077 AN: 152188 Hom.: 3576 Cov.: 32 AF XY: 0.205 AC XY: 15231 AN XY: 74406

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.0530

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.229

Alfa AF: 0.167 Hom.: 3061

Bravo AF: 0.215

Asia WGS AF: 0.0930 AC: 326 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	0.29
DANN	Benign	0.38

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: rs39335; hg19: chr7-103453569;