7-103630182-GAA-GA

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS1

The NM_005045.4(RELN):c.2466-7del 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 0.00989 in 1,206,504 control chromosomes in the GnomAD database, including 11 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.011 (11 hom.)
• Consequence: RELN NM_005045.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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 -12 ACMG points.

• BP6: Variant 7-103630182-GA-G is Benign according to our data. Variant chr7-103630182-GA-G is described in ClinVar as [Benign]. Clinvar id is 586401.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-103630182-GA-G is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00109 (151/138586) while in subpopulation EAS AF= 0.00966 (46/4760). AF 95% confidence interval is 0.00744. There are 0 homozygotes in gnomad4. There are 83 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RELN	NM_005045.4	c.2466-7del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000428762.6
RELN	NM_173054.3	c.2466-7del		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.2466-7del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_005045.4	P5

Frequencies

GnomAD3 genomes AF: 0.00108 AC: 149 AN: 138524 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000770

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00964

Gnomad SAS AF: 0.00585

Gnomad FIN AF: 0.000628

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000614

Gnomad OTH AF: 0.00108

GnomAD4 exome AF: 0.0110 AC: 11778 AN: 1067918 Hom.: 11 Cov.: 23 AF XY: 0.0106 AC XY: 5655 AN XY: 531030

Gnomad4 AFR exome AF: 0.0119

Gnomad4 AMR exome AF: 0.00860

Gnomad4 ASJ exome AF: 0.00662

Gnomad4 EAS exome AF: 0.0214

Gnomad4 SAS exome AF: 0.0120

Gnomad4 FIN exome AF: 0.0114

Gnomad4 NFE exome AF: 0.0108

Gnomad4 OTH exome AF: 0.0101

GnomAD4 genome AF: 0.00109 AC: 151 AN: 138586 Hom.: 0 Cov.: 32 AF XY: 0.00124 AC XY: 83 AN XY: 67058

Gnomad4 AFR AF: 0.000795

Gnomad4 AMR AF: 0.000216

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00966

Gnomad4 SAS AF: 0.00611

Gnomad4 FIN AF: 0.000628

Gnomad4 NFE AF: 0.000598

Gnomad4 OTH AF: 0.00106

Alfa AF: 0.0187 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Apr 05, 2018

- -

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;