rs6951931

chr7-103767839-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.544+8718G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,088 control chromosomes in the GnomAD database, including 3,273 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 (3273 hom., cov: 32)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RELN	NM_005045.4	c.544+8718G>A		intron_variant		ENST00000428762.6
RELN	NM_173054.3	c.544+8718G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELN	ENST00000428762.6	c.544+8718G>A		intron_variant		5	NM_005045.4	P5

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30697 AN: 151970 Hom.: 3276 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.0718

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.202 AC: 30704 AN: 152088 Hom.: 3273 Cov.: 32 AF XY: 0.202 AC XY: 15033 AN XY: 74332

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.0719

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.234

Alfa AF: 0.194 Hom.: 1651

Bravo AF: 0.209

Asia WGS AF: 0.106 AC: 369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.8
Dann	Benign	0.80

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: rs6951931; hg19: chr7-103408286;