rs79193208

chr7-103492056-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005045.4(RELN):c.9370-30C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0021 in 1,521,998 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (27 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (24 hom.)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.616

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=-0.82).
• BP6: Variant 7-103492056-G-C is Benign according to our data. Variant chr7-103492056-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 259618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0111 (1682/152102) while in subpopulation AFR AF= 0.0386 (1602/41474). AF 95% confidence interval is 0.0371. There are 27 homozygotes in gnomad4. There are 810 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 28 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RELN	NM_005045.4	c.9370-30C>G		intron_variant		ENST00000428762.6
SLC26A5-AS1	NR_110141.1	n.1366-12348G>C		intron_variant, non_coding_transcript_variant
RELN	NM_173054.3	c.9370-30C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELN	ENST00000428762.6	c.9370-30C>G		intron_variant		5	NM_005045.4	P5
SLC26A5-AS1	ENST00000422488.1	n.1366-12348G>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1679 AN: 151984 Hom.: 28 Cov.: 32

Gnomad AFR AF: 0.0387

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00354

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00277 AC: 659 AN: 237668 Hom.: 14 AF XY: 0.00205 AC XY: 263 AN XY: 128038

Gnomad AFR exome AF: 0.0402

Gnomad AMR exome AF: 0.00144

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000348

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000282

Gnomad OTH exome AF: 0.00102

GnomAD4 exome AF: 0.00110 AC: 1511 AN: 1369896 Hom.: 24 Cov.: 22 AF XY: 0.000958 AC XY: 657 AN XY: 685744

Gnomad4 AFR exome AF: 0.0401

Gnomad4 AMR exome AF: 0.00183

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000108

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000970

Gnomad4 OTH exome AF: 0.00235

GnomAD4 genome AF: 0.0111 AC: 1682 AN: 152102 Hom.: 27 Cov.: 32 AF XY: 0.0109 AC XY: 810 AN XY: 74348

Gnomad4 AFR AF: 0.0386

Gnomad4 AMR AF: 0.00353

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00632 Hom.: 3

Bravo AF: 0.0125

Asia WGS AF: 0.00115 AC: 4 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

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	5.4
Dann	Benign	0.53

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: rs79193208; hg19: chr7-103132503;