7-103886922-C-T

Position:

• chr7-103886922-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.337+30153G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 152,108 control chromosomes in the GnomAD database, including 46,689 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 0.78 (46689 hom., cov: 33)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225

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 (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RELN	NM_005045.4	c.337+30153G>A		intron_variant		ENST00000428762.6
RELN	NM_173054.3	c.337+30153G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELN	ENST00000428762.6	c.337+30153G>A		intron_variant		5	NM_005045.4	P5

Frequencies

GnomAD3 genomes AF: 0.783 AC: 119006 AN: 151992 Hom.: 46632 Cov.: 33

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.735

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

GnomAD4 genome AF: 0.783 AC: 119128 AN: 152108 Hom.: 46689 Cov.: 33 AF XY: 0.783 AC XY: 58186 AN XY: 74356

Gnomad4 AFR AF: 0.773

Gnomad4 AMR AF: 0.741

Gnomad4 ASJ AF: 0.697

Gnomad4 EAS AF: 0.869

Gnomad4 SAS AF: 0.857

Gnomad4 FIN AF: 0.754

Gnomad4 NFE AF: 0.798

Gnomad4 OTH AF: 0.736

Alfa AF: 0.787 Hom.: 108099

Bravo AF: 0.775

Asia WGS AF: 0.868 AC: 3019 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	1.1
DANN	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3914132; hg19: chr7-103527369;