7-103661529-TA-TAAAA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_005045.4(RELN):c.1290-3_1290-2insTTT 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 0.0000188 in 1,438,126 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: RELN NM_005045.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Likely 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 -2 ACMG points.

• BP6: Variant 7-103661529-T-TAAA is Benign according to our data. Variant chr7-103661529-T-TAAA is described in ClinVar as [Likely_benign]. Clinvar id is 1155534.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RELN	NM_005045.4	c.1290-3_1290-2insTTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000428762.6
RELN	NM_173054.3	c.1290-3_1290-2insTTT		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.1290-3_1290-2insTTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_005045.4	P5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000188 AC: 27 AN: 1438126 Hom.: 0 Cov.: 32 AF XY: 0.0000237 AC XY: 17 AN XY: 716072

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000237

Gnomad4 OTH exome AF: 0.0000169

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Sep 15, 2020

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Computational scores

Source: dbNSFP v4.3

Splicing

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;