rs146986040

chr7-103661529-TA-Tchr7-103661529-TA-TAAchr7-103661529-TA-TAAAchr7-103661529-TA-TAAAAchr7-103661529-TA-TAAAAAAAAchr7-103661529-TA-TAAAAAAAAA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS1

The NM_005045.4(RELN):c.1290-3del 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 0.000176 in 1,583,632 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 0.000073 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: RELN NM_005045.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.140

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 7-103661529-TA-T is Benign according to our data. Variant chr7-103661529-TA-T is described in ClinVar as [Benign]. Clinvar id is 542592.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-103661529-TA-T is described in Lovd as [Likely_benign]. Variant chr7-103661529-TA-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0000733 (11/150008) while in subpopulation AFR AF= 0.000147 (6/40894). AF 95% confidence interval is 0.0000635. There are 0 homozygotes in gnomad4. There are 4 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.1290-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000428762.6
RELN	NM_173054.3	c.1290-3del		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.1290-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_005045.4	P5

Frequencies

GnomAD3 genomes AF: 0.0000733 AC: 11 AN: 150008 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000742

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000187 AC: 268 AN: 1433624 Hom.: 0 Cov.: 32 AF XY: 0.000192 AC XY: 137 AN XY: 713968

Gnomad4 AFR exome AF: 0.000154

Gnomad4 AMR exome AF: 0.0000467

Gnomad4 ASJ exome AF: 0.0000391

Gnomad4 EAS exome AF: 0.0000257

Gnomad4 SAS exome AF: 0.0000707

Gnomad4 FIN exome AF: 0.000133

Gnomad4 NFE exome AF: 0.000217

Gnomad4 OTH exome AF: 0.000135

GnomAD4 genome AF: 0.0000733 AC: 11 AN: 150008 Hom.: 0 Cov.: 32 AF XY: 0.0000547 AC XY: 4 AN XY: 73184

Gnomad4 AFR AF: 0.000147

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000742

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000366 Hom.: 0

Bravo AF: 0.0000680

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 15, 2023

- -

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: rs146986040; hg19: chr7-103301976;