rs13223714

Positions:

• chr7-103849973-T-C
• chr7-103849973-T-G

Variant summary

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

The NM_005045.4(RELN):​c.338-16301A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,066 control chromosomes in the GnomAD database, including 7,383 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 0.30 (7383 hom., cov: 32)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RELN	NM_005045.4	c.338-16301A>G		intron_variant		ENST00000428762.6
RELN	NM_173054.3	c.338-16301A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELN	ENST00000428762.6	c.338-16301A>G		intron_variant		5	NM_005045.4	P5

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45688 AN: 151948 Hom.: 7359 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.301 AC: 45775 AN: 152066 Hom.: 7383 Cov.: 32 AF XY: 0.308 AC XY: 22862 AN XY: 74336

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.622

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.289

Alfa AF: 0.275 Hom.: 12475

Bravo AF: 0.299

Asia WGS AF: 0.543 AC: 1888 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.30
DANN	Benign	0.44

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: rs13223714; hg19: chr7-103490420;