rs12671505

Variant names:

• chr7-103516985-C-T
• rs12671505
• NM_005045.4:c.7863-1544G>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.7863-1544G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0554 in 152,156 control chromosomes in the GnomAD database, including 314 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 0.055 (314 hom., cov: 31)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• 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]

SLC26A5-AS1 (HGNC:55680): (SLC26A5 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RELN	NM_005045.4	c.7863-1544G>A		intron_variant	Intron 49 of 64	ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.7863-1544G>A		intron_variant	Intron 49 of 63		NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.7863-1544G>A		intron_variant	Intron 49 of 64	5	NM_005045.4	ENSP00000392423.1

Frequencies

GnomAD3 genomes AF: 0.0554 AC: 8418 AN: 152038 Hom.: 315 Cov.: 31

Gnomad AFR AF: 0.0271

Gnomad AMI AF: 0.0793

Gnomad AMR AF: 0.0812

Gnomad ASJ AF: 0.0620

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.0369

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0562

Gnomad OTH AF: 0.0589

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

GnomAD4 genome AF: 0.0554 AC: 8432 AN: 152156 Hom.: 314 Cov.: 31 AF XY: 0.0587 AC XY: 4369 AN XY: 74392

African (AFR) AF: 0.0270 AC: 1122 AN: 41510

American (AMR) AF: 0.0815 AC: 1246 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0620 AC: 215 AN: 3470

East Asian (EAS) AF: 0.126 AC: 653 AN: 5172

South Asian (SAS) AF: 0.160 AC: 772 AN: 4822

European-Finnish (FIN) AF: 0.0369 AC: 391 AN: 10590

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0562 AC: 3820 AN: 67996

Other (OTH) AF: 0.0621 AC: 131 AN: 2110

Alfa AF: 0.0476 Hom.: 83

Bravo AF: 0.0545

Asia WGS AF: 0.152 AC: 530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.16
DANN	Benign	0.43
PhyloP100		-2.8
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: rs12671505; hg19: chr7-103157432;