rs7791481

Positions:

• chr7-103864399-G-C

Variant summary

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

The NM_005045.4(RELN):​c.338-30727C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,170 control chromosomes in the GnomAD database, including 1,878 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 0.14 (1878 hom., cov: 33)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RELN	NM_005045.4	c.338-30727C>G		intron_variant		ENST00000428762.6
RELN	NM_173054.3	c.338-30727C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELN	ENST00000428762.6	c.338-30727C>G		intron_variant		5	NM_005045.4	P5

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21857 AN: 152052 Hom.: 1871 Cov.: 33

Gnomad AFR AF: 0.0670

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.144 AC: 21885 AN: 152170 Hom.: 1878 Cov.: 33 AF XY: 0.149 AC XY: 11082 AN XY: 74374

Gnomad4 AFR AF: 0.0670

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.133

Alfa AF: 0.145 Hom.: 215

Bravo AF: 0.134

Asia WGS AF: 0.310 AC: 1075 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.98
DANN	Benign	0.68

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: rs7791481; hg19: chr7-103504846;