NM_005045.4:c.9369+739G>A

Variant names:

• chr7-103494984-C-T
• rs2711881
• NM_005045.4:c.9369+739G>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.9369+739G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,722 control chromosomes in the GnomAD database, including 18,567 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 0.46 (18567 hom., cov: 30)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 5 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 (AFR) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RELN	NM_005045.4	c.9369+739G>A		intron_variant	Intron 57 of 64	ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.9369+739G>A		intron_variant	Intron 57 of 63		NP_774959.1
SLC26A5-AS1	NR_110141.1	n.1366-9420C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.9369+739G>A		intron_variant	Intron 57 of 64	5	NM_005045.4	ENSP00000392423.1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69074 AN: 151602 Hom.: 18515 Cov.: 30

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.456 AC: 69196 AN: 151722 Hom.: 18567 Cov.: 30 AF XY: 0.459 AC XY: 34043 AN XY: 74118

African (AFR) AF: 0.753 AC: 31191 AN: 41406

American (AMR) AF: 0.360 AC: 5481 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 968 AN: 3460

East Asian (EAS) AF: 0.545 AC: 2796 AN: 5132

South Asian (SAS) AF: 0.484 AC: 2321 AN: 4798

European-Finnish (FIN) AF: 0.375 AC: 3943 AN: 10508

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21298 AN: 67872

Other (OTH) AF: 0.410 AC: 865 AN: 2108

Alfa AF: 0.347 Hom.: 13375

Bravo AF: 0.464

Asia WGS AF: 0.568 AC: 1974 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	0.013
DANN	Benign	0.56
PhyloP100		-1.4
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: rs2711881; hg19: chr7-103135431;