7-103472549-A-T

Variant names:

• chr7-103472549-A-T
• rs879136898
• NM_005045.4:c.*263T>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005045.4(RELN):​c.*263T>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00000344 in 290,900 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: RELN NM_005045.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.42
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.18).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RELN	NM_005045.4	c.*263T>A		3_prime_UTR_variant	Exon 65 of 65	ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.*263T>A		3_prime_UTR_variant	Exon 64 of 64		NP_774959.1
SLC26A5-AS1	NR_110141.1	n.1365+25881A>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.*263T>A		3_prime_UTR_variant	Exon 65 of 65	5	NM_005045.4	ENSP00000392423.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000344 AC: 1 AN: 290900 Hom.: 0 Cov.: 0 AF XY: 0.00000649 AC XY: 1 AN XY: 153984

African (AFR) AF: 0.00 AC: 0 AN: 9014

American (AMR) AF: 0.00 AC: 0 AN: 11538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9042

East Asian (EAS) AF: 0.00 AC: 0 AN: 18102

South Asian (SAS) AF: 0.00 AC: 0 AN: 35592

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15904

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1194

European-Non Finnish (NFE) AF: 0.00000575 AC: 1 AN: 173784

Other (OTH) AF: 0.00 AC: 0 AN: 16730

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.18
CADD	Benign	17
DANN	Benign	0.90
PhyloP100		6.4

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: rs879136898; hg19: chr7-103112996;