rs73714429

Variant names:

• chr7-103511026-T-G
• rs73714429
• NM_005045.4:c.8120-21A>C

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: 0.121
• Publications: 1 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 -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 Benign/Likely_benign. ClinVar VariationId is 259614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RELN	NM_005045.4	c.8120-21A>C		intron_variant	Intron 50 of 64	ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.8120-21A>C		intron_variant	Intron 50 of 63		NP_774959.1
SLC26A5-AS1	NR_110141.1	n.1487-1743T>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.8120-21A>C		intron_variant	Intron 50 of 64	5	NM_005045.4	ENSP00000392423.1

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

GnomAD2 exomes AF: 0.0108 AC: 2676 AN: 246870 AF XY: 0.00786

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 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

African (AFR) AF: 0.153 AC: 5061 AN: 33168

American (AMR) AF: 0.00812 AC: 361 AN: 44470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26030

East Asian (EAS) AF: 0.00 AC: 0 AN: 39546

South Asian (SAS) AF: 0.000350 AC: 30 AN: 85646

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53308

Middle Eastern (MID) AF: 0.00749 AC: 43 AN: 5744

European-Non Finnish (NFE) AF: 0.000251 AC: 276 AN: 1101520

Other (OTH) AF: 0.00952 AC: 571 AN: 59994

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

African (AFR) AF: 0.140 AC: 5830 AN: 41506

American (AMR) AF: 0.0162 AC: 248 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000514 AC: 35 AN: 68028

Other (OTH) AF: 0.0351 AC: 74 AN: 2108

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.61
PhyloP100		0.12
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: rs73714429; hg19: chr7-103151473;