rs7791481

Variant names:

• chr7-103864399-G-C
• rs7791481
• NM_005045.4:c.338-30727C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005045.4(RELN):​c.338-30727C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,170 control chromosomes in the GnomAD database, including 1,878 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1878 hom., cov: 33)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RELN	NM_005045.4	c.338-30727C>G		intron_variant	Intron 2 of 64	ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.338-30727C>G		intron_variant	Intron 2 of 63		NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.338-30727C>G		intron_variant	Intron 2 of 64	5	NM_005045.4	ENSP00000392423.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21857 AN: 152052 Hom.: 1871 Cov.: 33

Gnomad AFR AF: 0.0670

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.144 AC: 21885 AN: 152170 Hom.: 1878 Cov.: 33 AF XY: 0.149 AC XY: 11082 AN XY: 74374

African (AFR) AF: 0.0670 AC: 2784 AN: 41556

American (AMR) AF: 0.145 AC: 2218 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 586 AN: 3470

East Asian (EAS) AF: 0.341 AC: 1761 AN: 5160

South Asian (SAS) AF: 0.328 AC: 1582 AN: 4824

European-Finnish (FIN) AF: 0.194 AC: 2050 AN: 10574

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10468 AN: 67998

Other (OTH) AF: 0.133 AC: 280 AN: 2110

Alfa AF: 0.145 Hom.: 215

Bravo AF: 0.134

Asia WGS AF: 0.310 AC: 1075 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.98
DANN	Benign	0.68
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7791481; hg19: chr7-103504846;