7-103989356-T-TGCCGCCGCC

Position:

• chr7-103989356-T-TGCCGCCGCC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_005045.4(RELN):​c.-9_-1dupGGCGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00678 in 1,407,470 control chromosomes in the GnomAD database, including 101 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (15 hom., cov: 0)
  • Exomes 𝑓: 0.0064 (86 hom.)
• Consequence: RELN NM_005045.4 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.06

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]

RELN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 7-103989356-T-TGCCGCCGCC is Benign according to our data. Variant chr7-103989356-T-TGCCGCCGCC is described in ClinVar as [Likely_benign]. Clinvar id is 193298.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.01 (1483/148348) while in subpopulation AFR AF= 0.0177 (712/40308). AF 95% confidence interval is 0.0166. There are 15 homozygotes in gnomad4. There are 745 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 15 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELN	NM_005045.4	c.-9_-1dupGGCGGCGGC		5_prime_UTR_variant	1/65	ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.-9_-1dupGGCGGCGGC		5_prime_UTR_variant	1/64		NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.-9_-1dupGGCGGCGGC		5_prime_UTR_variant	1/65	5	NM_005045.4	ENSP00000392423.1

Frequencies

GnomAD3 genomes AF: 0.00997 AC: 1478 AN: 148250 Hom.: 13 Cov.: 0

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00512

Gnomad ASJ AF: 0.00842

Gnomad EAS AF: 0.00721

Gnomad SAS AF: 0.00426

Gnomad FIN AF: 0.0133

Gnomad MID AF: 0.0101

Gnomad NFE AF: 0.00680

Gnomad OTH AF: 0.00982

GnomAD4 exome AF: 0.00640 AC: 8058 AN: 1259122 Hom.: 86 Cov.: 36 AF XY: 0.00617 AC XY: 3827 AN XY: 620182

Gnomad4 AFR exome AF: 0.0145

Gnomad4 AMR exome AF: 0.00250

Gnomad4 ASJ exome AF: 0.00447

Gnomad4 EAS exome AF: 0.00919

Gnomad4 SAS exome AF: 0.00260

Gnomad4 FIN exome AF: 0.0129

Gnomad4 NFE exome AF: 0.00614

Gnomad4 OTH exome AF: 0.00803

GnomAD4 genome AF: 0.0100 AC: 1483 AN: 148348 Hom.: 15 Cov.: 0 AF XY: 0.0103 AC XY: 745 AN XY: 72348

Gnomad4 AFR AF: 0.0177

Gnomad4 AMR AF: 0.00512

Gnomad4 ASJ AF: 0.00842

Gnomad4 EAS AF: 0.00724

Gnomad4 SAS AF: 0.00426

Gnomad4 FIN AF: 0.0133

Gnomad4 NFE AF: 0.00680

Gnomad4 OTH AF: 0.00971

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 05, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Oct 25, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 20, 2018

- -

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: rs55656324; hg19: chr7-103629803;