7-103936441-T-G

Variant names:

• chr7-103936441-T-G
• rs12705169
• NM_005045.4:c.227-19256A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005045.4(RELN):​c.227-19256A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 151,984 control chromosomes in the GnomAD database, including 5,739 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 0.25 (5739 hom., cov: 31)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.303

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RELN	NM_005045.4	c.227-19256A>C		intron_variant	Intron 1 of 64	ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.227-19256A>C		intron_variant	Intron 1 of 63		NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.227-19256A>C		intron_variant	Intron 1 of 64	5	NM_005045.4	ENSP00000392423.1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37245 AN: 151864 Hom.: 5741 Cov.: 31

Gnomad AFR AF: 0.0639

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.245 AC: 37246 AN: 151984 Hom.: 5739 Cov.: 31 AF XY: 0.246 AC XY: 18307 AN XY: 74282

Gnomad4 AFR AF: 0.0637

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.224

Alfa AF: 0.210 Hom.: 726

Bravo AF: 0.225

Asia WGS AF: 0.193 AC: 671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.38
DANN	Benign	0.86

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: rs12705169; hg19: chr7-103576888;