7-103936441-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005045.4(RELN):​c.227-19256A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 151,984 control chromosomes in the GnomAD database, including 5,739 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5739 hom., cov: 31)

Consequence

RELN
NM_005045.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.303
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RELNNM_005045.4 linkc.227-19256A>C intron_variant Intron 1 of 64 ENST00000428762.6 NP_005036.2 P78509-1
RELNNM_173054.3 linkc.227-19256A>C intron_variant Intron 1 of 63 NP_774959.1 P78509-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RELNENST00000428762.6 linkc.227-19256A>C intron_variant Intron 1 of 64 5 NM_005045.4 ENSP00000392423.1 P78509-1

Frequencies

GnomAD3 genomes
AF:
0.245
AC:
37245
AN:
151864
Hom.:
5741
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0639
Gnomad AMI
AF:
0.496
Gnomad AMR
AF:
0.235
Gnomad ASJ
AF:
0.233
Gnomad EAS
AF:
0.185
Gnomad SAS
AF:
0.206
Gnomad FIN
AF:
0.384
Gnomad MID
AF:
0.201
Gnomad NFE
AF:
0.342
Gnomad OTH
AF:
0.225
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.245
AC:
37246
AN:
151984
Hom.:
5739
Cov.:
31
AF XY:
0.246
AC XY:
18307
AN XY:
74282
show subpopulations
Gnomad4 AFR
AF:
0.0637
Gnomad4 AMR
AF:
0.235
Gnomad4 ASJ
AF:
0.233
Gnomad4 EAS
AF:
0.186
Gnomad4 SAS
AF:
0.207
Gnomad4 FIN
AF:
0.384
Gnomad4 NFE
AF:
0.342
Gnomad4 OTH
AF:
0.224
Alfa
AF:
0.210
Hom.:
726
Bravo
AF:
0.225
Asia WGS
AF:
0.193
AC:
671
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.71
CADD
Benign
0.38
DANN
Benign
0.86

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs12705169; hg19: chr7-103576888; API