rs2072402

Positions:

• chr7-103651474-C-A
• chr7-103651474-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005045.4(RELN):​c.1892+187G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0938 in 152,064 control chromosomes in the GnomAD database, including 948 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.094 (948 hom., cov: 33)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.546

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-103651474-C-A is Benign according to our data. Variant chr7-103651474-C-A is described in ClinVar as [Benign]. Clinvar id is 1269601.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELN	NM_005045.4	c.1892+187G>T		intron_variant		ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.1892+187G>T		intron_variant			NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.1892+187G>T		intron_variant		5	NM_005045.4	ENSP00000392423	P5

Frequencies

GnomAD3 genomes AF: 0.0936 AC: 14222 AN: 151946 Hom.: 941 Cov.: 33

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0763

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.0365

Gnomad FIN AF: 0.0815

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.0478

Gnomad OTH AF: 0.0789

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0938 AC: 14259 AN: 152064 Hom.: 948 Cov.: 33 AF XY: 0.0942 AC XY: 6999 AN XY: 74336

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.0762

Gnomad4 ASJ AF: 0.0441

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.0359

Gnomad4 FIN AF: 0.0815

Gnomad4 NFE AF: 0.0478

Gnomad4 OTH AF: 0.0795

Alfa AF: 0.0443 Hom.: 76

Bravo AF: 0.100

Asia WGS AF: 0.0920 AC: 318 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.88
DANN	Benign	0.071

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: rs2072402; hg19: chr7-103291921;