rs2072402

Variant names:

• chr7-103651474-C-A
• rs2072402
• NM_005045.4:c.1892+187G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• lissencephaly with cerebellar hypoplasia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Norman-Roberts syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P, PanelApp Australia
• familial temporal lobe epilepsy 7

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal dominant epilepsy with auditory features

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• ankylosing spondylitis

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
RELN	NM_005045.4	c.1892+187G>T		intron_variant	Intron 15 of 64	ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.1892+187G>T		intron_variant	Intron 15 of 63		NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.1892+187G>T		intron_variant	Intron 15 of 64	5	NM_005045.4	ENSP00000392423.1

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

African (AFR) AF: 0.186 AC: 7711 AN: 41496

American (AMR) AF: 0.0762 AC: 1163 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0441 AC: 153 AN: 3466

East Asian (EAS) AF: 0.137 AC: 708 AN: 5150

South Asian (SAS) AF: 0.0359 AC: 173 AN: 4824

European-Finnish (FIN) AF: 0.0815 AC: 863 AN: 10594

Middle Eastern (MID) AF: 0.0240 AC: 7 AN: 292

European-Non Finnish (NFE) AF: 0.0478 AC: 3250 AN: 67962

Other (OTH) AF: 0.0795 AC: 168 AN: 2112

Alfa AF: 0.0606 Hom.: 211

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

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.88
DANN	Benign	0.071
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2072402; hg19: chr7-103291921;