Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005045.4(RELN):c.9903C>T(p.Tyr3301Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 1,614,150 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 32 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 28 hom. )

Consequence

RELN
NM_005045.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.193

Publications

2 publications found

Variant links:

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]

RELN links:

SLC26A5-AS1 (HGNC:55680): (SLC26A5 antisense RNA 1)

SLC26A5-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 7-103486277-G-A is Benign according to our data. Variant chr7-103486277-G-A is described in ClinVar as Benign. ClinVar VariationId is 130147.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.193 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0127 (1932/152290) while in subpopulation AFR AF = 0.0438 (1818/41548). AF 95% confidence interval is 0.0421. There are 32 homozygotes in GnomAd4. There are 909 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 32 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005045.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RELN	NM_005045.4	MANE Select	c.9903C>T	p.Tyr3301Tyr	synonymous	Exon 61 of 65	NP_005036.2
RELN	NM_173054.3		c.9903C>T	p.Tyr3301Tyr	synonymous	Exon 61 of 64	NP_774959.1
SLC26A5-AS1	NR_110141.1		n.1366-18127G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RELN	ENST00000428762.6	TSL:5 MANE Select	c.9903C>T	p.Tyr3301Tyr	synonymous	Exon 61 of 65	ENSP00000392423.1
SLC26A5-AS1	ENST00000422488.1	TSL:1	n.1366-18127G>A		intron	N/A
RELN	ENST00000424685.3	TSL:5	c.9903C>T	p.Tyr3301Tyr	synonymous	Exon 61 of 65	ENSP00000388446.3

Frequencies

GnomAD3 genomes

AF:

0.0127

AC:

1931

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0439

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00957

GnomAD2 exomes

AF:

0.00335

AC:

843

AN:

251306

AF XY:

0.00251

show subpopulations

Gnomad AFR exome

AF:

0.0434

Gnomad AMR exome

AF:

0.00226

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000238

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00128

AC:

1866

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

826

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.0422

AC:

1414

AN:

33478

American (AMR)

AF:

0.00237

AC:

106

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39698

South Asian (SAS)

AF:

0.000800

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000953

AC:

106

AN:

1111992

Other (OTH)

AF:

0.00260

AC:

157

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

110

221

331

442

552

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0127

AC:

1932

AN:

152290

Hom.:

Cov.:

AF XY:

0.0122

AC XY:

909

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0438

AC:

1818

AN:

41548

American (AMR)

AF:

0.00503

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.000622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68026

Other (OTH)

AF:

0.00947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

180

269

359

449

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00509

Hom.:

Bravo

AF:

0.0142

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Norman-Roberts syndrome (1)

Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7 (1)

RELN-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

1.7

(source)

DANN

Benign

0.76

PhyloP100

-0.19

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs73714404

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over