rs777843062

Variant names:

• chr7-103510930-C-A
• rs777843062
• NM_005045.4:c.8195G>T
• RELN p.Cys2732Phe

Your query was ambiguous. Multiple possible variants found:

• chr7-103510930-C-A
• chr7-103510930-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005045.4(RELN):​c.8195G>T​(p.Cys2732Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RELN NM_005045.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 6.57
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELN	NM_005045.4	MANE Select	c.8195G>T	p.Cys2732Phe	missense	Exon 51 of 65	NP_005036.2
	RELN	NM_173054.3		c.8195G>T	p.Cys2732Phe	missense	Exon 51 of 64	NP_774959.1	P78509-2
	SLC26A5-AS1	NR_110141.1		n.1487-1839C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELN	ENST00000428762.6	TSL:5 MANE Select	c.8195G>T	p.Cys2732Phe	missense	Exon 51 of 65	ENSP00000392423.1	P78509-1
	SLC26A5-AS1	ENST00000422488.1	TSL:1	n.1487-1839C>A		intron	N/A
	RELN	ENST00000424685.3	TSL:5	c.8195G>T	p.Cys2732Phe	missense	Exon 51 of 65	ENSP00000388446.3	J3KQ66

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460350 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726580

African (AFR) AF: 0.00 AC: 0 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110666

Other (OTH) AF: 0.00 AC: 0 AN: 60348

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Familial temporal lobe epilepsy 7 (1)
-	1	-	Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.59	N
PhyloP100		6.6
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.45
Sift	Benign	0.41	T
Sift4G	Uncertain	0.010	D
Varity_R		0.49
gMVP		0.71
Mutation Taster		=63/37	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs777843062;

hg19: chr7-103151377;