rs997447

chr7-103624929-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.2702+5011A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,220 control chromosomes in the GnomAD database, including 1,736 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 0.15 (1736 hom., cov: 33)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.980

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RELN	NM_005045.4	c.2702+5011A>G		intron_variant		ENST00000428762.6
RELN	NM_173054.3	c.2702+5011A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELN	ENST00000428762.6	c.2702+5011A>G		intron_variant		5	NM_005045.4	P5

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22443 AN: 152102 Hom.: 1733 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.0890

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0661

Gnomad SAS AF: 0.0914

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.148 AC: 22467 AN: 152220 Hom.: 1736 Cov.: 33 AF XY: 0.146 AC XY: 10883 AN XY: 74446

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.0659

Gnomad4 SAS AF: 0.0925

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.181

Alfa AF: 0.157 Hom.: 1448

Bravo AF: 0.157

Asia WGS AF: 0.0850 AC: 296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	7.0
Dann	Benign	0.45

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: rs997447; hg19: chr7-103265376;