rs73714429

chr7-103511026-T-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.8120-21A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00782 in 1,601,666 control chromosomes in the GnomAD database, including 808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (406 hom., cov: 32)
  • Exomes 𝑓: 0.0044 (402 hom.)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.121

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=-0.81).
• BP6: Variant 7-103511026-T-G is Benign according to our data. Variant chr7-103511026-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 259614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-103511026-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RELN	NM_005045.4	c.8120-21A>C		intron_variant		ENST00000428762.6
SLC26A5-AS1	NR_110141.1	n.1487-1743T>G		intron_variant, non_coding_transcript_variant
RELN	NM_173054.3	c.8120-21A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELN	ENST00000428762.6	c.8120-21A>C		intron_variant		5	NM_005045.4	P5
SLC26A5-AS1	ENST00000422488.1	n.1487-1743T>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0405 AC: 6160 AN: 152122 Hom.: 404 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0162

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000514

Gnomad OTH AF: 0.0355

GnomAD3 exomes AF: 0.0108 AC: 2676 AN: 246870 Hom.: 166 AF XY: 0.00786 AC XY: 1048 AN XY: 133398

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.00731

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000399

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000451

Gnomad OTH exome AF: 0.00593

GnomAD4 exome AF: 0.00438 AC: 6343 AN: 1449426 Hom.: 402 Cov.: 28 AF XY: 0.00382 AC XY: 2759 AN XY: 721520

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.00812

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000350

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000251

Gnomad4 OTH exome AF: 0.00952

GnomAD4 genome AF: 0.0407 AC: 6190 AN: 152240 Hom.: 406 Cov.: 32 AF XY: 0.0392 AC XY: 2915 AN XY: 74440

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.0162

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000514

Gnomad4 OTH AF: 0.0351

Alfa AF: 0.0228 Hom.: 39

Bravo AF: 0.0467

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	1.4
Dann	Benign	0.61

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: rs73714429; hg19: chr7-103151473;