7-103565554-GAA-GAAAA

Position:

• chr7-103565554-GAA-GAAAA

Variant summary

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

The NM_005045.4(RELN):​c.4937-4_4937-3insTT 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 0.00643 in 1,382,472 control chromosomes in the GnomAD database, including 19 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0054 (14 hom., cov: 0)
  • Exomes 𝑓: 0.0066 (5 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: 0.186

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 7-103565554-G-GAA is Benign according to our data. Variant chr7-103565554-G-GAA is described in ClinVar as [Benign]. Clinvar id is 475969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELN	NM_005045.4	c.4937-4_4937-3insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.4937-4_4937-3insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.4937-4_4937-3insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_005045.4	ENSP00000392423	P5

Frequencies

GnomAD3 genomes AF: 0.00540 AC: 799 AN: 147998 Hom.: 14 Cov.: 0

Gnomad AFR AF: 0.00176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0427

Gnomad ASJ AF: 0.00234

Gnomad EAS AF: 0.00118

Gnomad SAS AF: 0.000425

Gnomad FIN AF: 0.000105

Gnomad MID AF: 0.00325

Gnomad NFE AF: 0.000913

Gnomad OTH AF: 0.00735

GnomAD4 exome AF: 0.00656 AC: 8093 AN: 1234402 Hom.: 5 Cov.: 32 AF XY: 0.00607 AC XY: 3727 AN XY: 613978

Gnomad4 AFR exome AF: 0.00443

Gnomad4 AMR exome AF: 0.0658

Gnomad4 ASJ exome AF: 0.00500

Gnomad4 EAS exome AF: 0.00126

Gnomad4 SAS exome AF: 0.00251

Gnomad4 FIN exome AF: 0.00268

Gnomad4 NFE exome AF: 0.00506

Gnomad4 OTH exome AF: 0.00607

GnomAD4 genome AF: 0.00540 AC: 800 AN: 148070 Hom.: 14 Cov.: 0 AF XY: 0.00604 AC XY: 435 AN XY: 72046

Gnomad4 AFR AF: 0.00176

Gnomad4 AMR AF: 0.0427

Gnomad4 ASJ AF: 0.00234

Gnomad4 EAS AF: 0.00119

Gnomad4 SAS AF: 0.000426

Gnomad4 FIN AF: 0.000105

Gnomad4 NFE AF: 0.000913

Gnomad4 OTH AF: 0.00678

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Sep 05, 2014

- -

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Apr 13, 2015

- -

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: rs35268159; hg19: chr7-103206001;