chr7-103748638-T-C

Variant names:

• chr7-103748638-T-C
• rs528528
• NM_005045.4:c.656+788A>G

Variant summary

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

The NM_005045.4(RELN):​c.656+788A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 152,058 control chromosomes in the GnomAD database, including 19,202 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 0.50 (19202 hom., cov: 33)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RELN	NM_005045.4	c.656+788A>G		intron_variant	Intron 6 of 64	ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.656+788A>G		intron_variant	Intron 6 of 63		NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.656+788A>G		intron_variant	Intron 6 of 64	5	NM_005045.4	ENSP00000392423.1

Frequencies

GnomAD3 genomes AF: 0.500 AC: 76032 AN: 151940 Hom.: 19172 Cov.: 33

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.500 AC: 76102 AN: 152058 Hom.: 19202 Cov.: 33 AF XY: 0.496 AC XY: 36852 AN XY: 74326

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.543

Gnomad4 OTH AF: 0.521

Alfa AF: 0.539 Hom.: 32040

Bravo AF: 0.499

Asia WGS AF: 0.395 AC: 1372 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.65

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: rs528528; hg19: chr7-103389085;