7-103500904-G-C

Variant names:

• chr7-103500904-G-C
• rs2229862
• NM_005045.4:c.8508C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005045.4(RELN):​c.8508C>G​(p.Phe2836Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F2836F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RELN NM_005045.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.54
• Publications: 5 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36502114).

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.8508C>G	p.Phe2836Leu	missense	Exon 53 of 65	NP_005036.2
	RELN	NM_173054.3		c.8508C>G	p.Phe2836Leu	missense	Exon 53 of 64	NP_774959.1	P78509-2
	SLC26A5-AS1	NR_110141.1		n.1366-3500G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELN	ENST00000428762.6	TSL:5 MANE Select	c.8508C>G	p.Phe2836Leu	missense	Exon 53 of 65	ENSP00000392423.1	P78509-1
	SLC26A5-AS1	ENST00000422488.1	TSL:1	n.1366-3500G>C		intron	N/A
	RELN	ENST00000424685.3	TSL:5	c.8508C>G	p.Phe2836Leu	missense	Exon 53 of 65	ENSP00000388446.3	J3KQ66

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.049
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.42	N
PhyloP100		4.5
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.099
Sift	Benign	0.21	T
Sift4G	Benign	0.19	T
Polyphen		0.0	B
Vest4		0.56
MutPred		0.69		Gain of sheet (P = 0.0827)
MVP		0.21
MPC		0.35
ClinPred		0.75	D
GERP RS		4.3
Varity_R		0.24
gMVP		0.76
Mutation Taster		=68/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2229862; hg19: chr7-103141351;