7-103511004-C-T

Variant names:

• chr7-103511004-C-T
• rs1345247825
• NM_005045.4:c.8121G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6 BP7

The NM_005045.4(RELN):​c.8121G>A​(p.Val2707Val) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. V2707V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RELN NM_005045.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.005327
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 1.36
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 7-103511004-C-T is Benign according to our data. Variant chr7-103511004-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 436525.
• BP7: Synonymous conserved (PhyloP=1.36 with no splicing effect.

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.8121G>A	p.Val2707Val	splice_region synonymous	Exon 51 of 65	NP_005036.2
	RELN	NM_173054.3		c.8121G>A	p.Val2707Val	splice_region synonymous	Exon 51 of 64	NP_774959.1	P78509-2
	SLC26A5-AS1	NR_110141.1		n.1487-1765C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELN	ENST00000428762.6	TSL:5 MANE Select	c.8121G>A	p.Val2707Val	splice_region synonymous	Exon 51 of 65	ENSP00000392423.1	P78509-1
	SLC26A5-AS1	ENST00000422488.1	TSL:1	n.1487-1765C>T		intron	N/A
	RELN	ENST00000424685.3	TSL:5	c.8121G>A	p.Val2707Val	splice_region synonymous	Exon 51 of 65	ENSP00000388446.3	J3KQ66

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	1	Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7 (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	11
DANN	Benign	0.87
PhyloP100		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0053
dbscSNV1_RF	Benign	0.23
SpliceAI score (max)		0.020		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: rs1345247825; hg19: chr7-103151451;