7-103516928-C-T

Variant names:

• chr7-103516928-C-T
• rs2528865
• NM_005045.4:c.7863-1487G>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.7863-1487G>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 151,890 control chromosomes in the GnomAD database, including 5,076 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 (5076 hom., cov: 31)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266
• Publications: 2 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RELN	NM_005045.4	c.7863-1487G>A		intron_variant	Intron 49 of 64	ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.7863-1487G>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.7863-1487G>A		intron_variant	Intron 49 of 64	5	NM_005045.4	ENSP00000392423.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34637 AN: 151772 Hom.: 5071 Cov.: 31

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.228 AC: 34693 AN: 151890 Hom.: 5076 Cov.: 31 AF XY: 0.231 AC XY: 17174 AN XY: 74228

African (AFR) AF: 0.378 AC: 15661 AN: 41434

American (AMR) AF: 0.224 AC: 3422 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 509 AN: 3468

East Asian (EAS) AF: 0.515 AC: 2660 AN: 5162

South Asian (SAS) AF: 0.324 AC: 1560 AN: 4822

European-Finnish (FIN) AF: 0.117 AC: 1235 AN: 10518

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 292

European-Non Finnish (NFE) AF: 0.133 AC: 9032 AN: 67932

Other (OTH) AF: 0.222 AC: 468 AN: 2106

Alfa AF: 0.169 Hom.: 8199

Bravo AF: 0.239

Asia WGS AF: 0.432 AC: 1505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.96
DANN	Benign	0.62
PhyloP100		-0.27
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: rs2528865; hg19: chr7-103157375;