7-103630182-GAA-GAAA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_005045.4(RELN):c.2466-7_2466-6insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0622 in 1,051,372 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 32)
  • Exomes 𝑓: 0.072 (0 hom.)
• Consequence: RELN NM_005045.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.884

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 -16 ACMG points.

• BP6: Variant 7-103630182-G-GA is Benign according to our data. Variant chr7-103630182-G-GA is described in ClinVar as [Benign]. Clinvar id is 195496.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RELN	NM_005045.4	c.2466-7_2466-6insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000428762.6
RELN	NM_173054.3	c.2466-7_2466-6insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELN	ENST00000428762.6	c.2466-7_2466-6insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_005045.4	P5

Frequencies

GnomAD3 genomes AF: 0.000332 AC: 46 AN: 138474 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000292

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000288

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000209

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00138

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000284

Gnomad OTH AF: 0.000538

GnomAD4 exome AF: 0.0716 AC: 65364 AN: 912836 Hom.: 0 Cov.: 23 AF XY: 0.0697 AC XY: 31188 AN XY: 447198

Gnomad4 AFR exome AF: 0.0753

Gnomad4 AMR exome AF: 0.0517

Gnomad4 ASJ exome AF: 0.0726

Gnomad4 EAS exome AF: 0.0573

Gnomad4 SAS exome AF: 0.0488

Gnomad4 FIN exome AF: 0.0534

Gnomad4 NFE exome AF: 0.0746

Gnomad4 OTH exome AF: 0.0747

GnomAD4 genome AF: 0.000354 AC: 49 AN: 138536 Hom.: 0 Cov.: 32 AF XY: 0.000343 AC XY: 23 AN XY: 67028

Gnomad4 AFR AF: 0.000344

Gnomad4 AMR AF: 0.000288

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000210

Gnomad4 SAS AF: 0.000226

Gnomad4 FIN AF: 0.00138

Gnomad4 NFE AF: 0.000284

Gnomad4 OTH AF: 0.000532

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 14, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Oct 28, 2016	- -

Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 08, 2024

- -

Computational scores

Source: dbNSFP v4.3

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: rs571882672; hg19: chr7-103270629;