rs2106173

Positions:

• chr7-103694109-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.1143+3744G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 151,896 control chromosomes in the GnomAD database, including 3,861 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 (3861 hom., cov: 32)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RELN	NM_005045.4	c.1143+3744G>A		intron_variant		ENST00000428762.6
RELN	NM_173054.3	c.1143+3744G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELN	ENST00000428762.6	c.1143+3744G>A		intron_variant		5	NM_005045.4	P5

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30129 AN: 151778 Hom.: 3843 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.0966

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.199 AC: 30185 AN: 151896 Hom.: 3861 Cov.: 32 AF XY: 0.198 AC XY: 14671 AN XY: 74250

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.0966

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.189

Alfa AF: 0.166 Hom.: 417

Bravo AF: 0.213

Asia WGS AF: 0.199 AC: 690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.2
DANN	Benign	0.49

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: rs2106173; hg19: chr7-103334556;