7-103765070-C-T

Variant names:

• chr7-103765070-C-T
• rs10435342
• NM_005045.4:c.544+11487G>A

Variant summary

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

The NM_005045.4(RELN):​c.544+11487G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 151,928 control chromosomes in the GnomAD database, including 4,608 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 0.23 (4608 hom., cov: 31)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.870
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005045.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELN	NM_005045.4	MANE Select	c.544+11487G>A		intron	N/A	NP_005036.2
	RELN	NM_173054.3		c.544+11487G>A		intron	N/A	NP_774959.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELN	ENST00000428762.6	TSL:5 MANE Select	c.544+11487G>A		intron	N/A	ENSP00000392423.1
	RELN	ENST00000424685.3	TSL:5	c.544+11487G>A		intron	N/A	ENSP00000388446.3
	RELN	ENST00000343529.9	TSL:5	c.544+11487G>A		intron	N/A	ENSP00000345694.5

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34602 AN: 151812 Hom.: 4609 Cov.: 31

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.0711

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.228 AC: 34619 AN: 151928 Hom.: 4608 Cov.: 31 AF XY: 0.227 AC XY: 16818 AN XY: 74234

African (AFR) AF: 0.357 AC: 14786 AN: 41436

American (AMR) AF: 0.237 AC: 3617 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 730 AN: 3466

East Asian (EAS) AF: 0.0713 AC: 368 AN: 5162

South Asian (SAS) AF: 0.118 AC: 568 AN: 4800

European-Finnish (FIN) AF: 0.227 AC: 2387 AN: 10530

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11338 AN: 67952

Other (OTH) AF: 0.248 AC: 522 AN: 2108

Alfa AF: 0.221 Hom.: 625

Bravo AF: 0.242

Asia WGS AF: 0.114 AC: 396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.75
DANN	Benign	0.82
PhyloP100		-0.87
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: rs10435342; hg19: chr7-103405517;