7-103734819-C-T

Variant names:

• chr7-103734819-C-T
• rs10487166
• NM_005045.4:c.657-6612G>A

Variant summary

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

The NM_005045.4(RELN):​c.657-6612G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,152 control chromosomes in the GnomAD database, including 945 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 0.11 (945 hom., cov: 32)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.741

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RELN	NM_005045.4	c.657-6612G>A		intron_variant	Intron 6 of 64	ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.657-6612G>A		intron_variant	Intron 6 of 63		NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.657-6612G>A		intron_variant	Intron 6 of 64	5	NM_005045.4	ENSP00000392423.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16654 AN: 152034 Hom.: 949 Cov.: 32

Gnomad AFR AF: 0.0935

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.0778

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.109 AC: 16648 AN: 152152 Hom.: 945 Cov.: 32 AF XY: 0.110 AC XY: 8175 AN XY: 74392

Gnomad4 AFR AF: 0.0933

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.0778

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.113

Alfa AF: 0.0807 Hom.: 154

Bravo AF: 0.110

Asia WGS AF: 0.164 AC: 571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
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: rs10487166; hg19: chr7-103375266;