rs362719

Variant names:

• chr7-103545430-C-A
• rs362719
• NM_005045.4:c.6303-86G>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005045.4(RELN):​c.6303-86G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 889,372 control chromosomes in the GnomAD database, including 32,776 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (10356 hom., cov: 32)
  • Exomes 𝑓: 0.23 (22420 hom.)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.90

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-103545430-C-A is Benign according to our data. Variant chr7-103545430-C-A is described in ClinVar as [Benign]. Clinvar id is 674180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RELN	NM_005045.4	c.6303-86G>T		intron_variant	Intron 41 of 64	ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.6303-86G>T		intron_variant	Intron 41 of 63		NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.6303-86G>T		intron_variant	Intron 41 of 64	5	NM_005045.4	ENSP00000392423.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48605 AN: 151920 Hom.: 10325 Cov.: 32

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.289

GnomAD4 exome AF: 0.227 AC: 167614 AN: 737334 Hom.: 22420 AF XY: 0.231 AC XY: 90012 AN XY: 390064

Gnomad4 AFR exome AF: 0.600

Gnomad4 AMR exome AF: 0.295

Gnomad4 ASJ exome AF: 0.212

Gnomad4 EAS exome AF: 0.344

Gnomad4 SAS exome AF: 0.375

Gnomad4 FIN exome AF: 0.215

Gnomad4 NFE exome AF: 0.178

Gnomad4 OTH exome AF: 0.247

GnomAD4 genome AF: 0.320 AC: 48706 AN: 152038 Hom.: 10356 Cov.: 32 AF XY: 0.324 AC XY: 24072 AN XY: 74302

Gnomad4 AFR AF: 0.600

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.294

Alfa AF: 0.202 Hom.: 7451

Bravo AF: 0.333

Asia WGS AF: 0.413 AC: 1436 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.047
DANN	Benign	0.28

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: rs362719; hg19: chr7-103185877;