rs736707

Positions:

• chr7-103489956-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005045.4(RELN):​c.9606-57T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 1,602,426 control chromosomes in the GnomAD database, including 50,574 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7625 hom., cov: 32)
  • Exomes 𝑓: 0.23 (42949 hom.)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.46

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 7-103489956-A-G is Benign according to our data. Variant chr7-103489956-A-G is described in ClinVar as [Benign]. Clinvar id is 1295479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELN	NM_005045.4	c.9606-57T>C		intron_variant		ENST00000428762.6	NP_005036.2
SLC26A5-AS1	NR_110141.1	n.1366-14448A>G		intron_variant, non_coding_transcript_variant
RELN	NM_173054.3	c.9606-57T>C		intron_variant			NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.9606-57T>C		intron_variant		5	NM_005045.4	ENSP00000392423	P5
SLC26A5-AS1	ENST00000422488.1	n.1366-14448A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44880 AN: 151858 Hom.: 7624 Cov.: 32

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.276

GnomAD4 exome AF: 0.232 AC: 337181 AN: 1450450 Hom.: 42949 AF XY: 0.236 AC XY: 170094 AN XY: 721946

Gnomad4 AFR exome AF: 0.466

Gnomad4 AMR exome AF: 0.221

Gnomad4 ASJ exome AF: 0.205

Gnomad4 EAS exome AF: 0.491

Gnomad4 SAS exome AF: 0.352

Gnomad4 FIN exome AF: 0.240

Gnomad4 NFE exome AF: 0.207

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.296 AC: 44922 AN: 151976 Hom.: 7625 Cov.: 32 AF XY: 0.298 AC XY: 22172 AN XY: 74310

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.275

Alfa AF: 0.225 Hom.: 8567

Bravo AF: 0.298

Asia WGS AF: 0.413 AC: 1436 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0030
DANN	Benign	0.26

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: rs736707; hg19: chr7-103130403; COSMIC: COSV58991874; COSMIC: COSV58991874;