7-103483760-T-C

Variant names:

• chr7-103483760-T-C
• rs1062831
• NM_005045.4:c.10074A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005045.4(RELN):​c.10074A>G​(p.Ala3358Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,613,946 control chromosomes in the GnomAD database, including 13,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (3281 hom., cov: 33)
  • Exomes 𝑓: 0.10 (10240 hom.)
• Consequence: RELN NM_005045.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -2.35
• Publications: 22 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 7-103483760-T-C is Benign according to our data. Variant chr7-103483760-T-C is described in ClinVar as Benign. ClinVar VariationId is 95209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.35 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELN	NM_005045.4	MANE Select	c.10074A>G	p.Ala3358Ala	synonymous	Exon 62 of 65	NP_005036.2
	RELN	NM_173054.3		c.10074A>G	p.Ala3358Ala	synonymous	Exon 62 of 64	NP_774959.1
	SLC26A5-AS1	NR_110141.1		n.1366-20644T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELN	ENST00000428762.6	TSL:5 MANE Select	c.10074A>G	p.Ala3358Ala	synonymous	Exon 62 of 65	ENSP00000392423.1
	SLC26A5-AS1	ENST00000422488.1	TSL:1	n.1366-20644T>C		intron	N/A
	RELN	ENST00000424685.3	TSL:5	c.10074A>G	p.Ala3358Ala	synonymous	Exon 62 of 65	ENSP00000388446.3

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26341 AN: 152128 Hom.: 3262 Cov.: 33

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0847

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.0546

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0924

Gnomad OTH AF: 0.163

GnomAD2 exomes AF: 0.132 AC: 33258 AN: 251074 AF XY: 0.130

Gnomad AFR exome AF: 0.351

Gnomad AMR exome AF: 0.111

Gnomad ASJ exome AF: 0.0857

Gnomad EAS exome AF: 0.274

Gnomad FIN exome AF: 0.0538

Gnomad NFE exome AF: 0.0935

Gnomad OTH exome AF: 0.106

GnomAD4 exome AF: 0.104 AC: 152127 AN: 1461700 Hom.: 10240 Cov.: 33 AF XY: 0.105 AC XY: 76713 AN XY: 727156

African (AFR) AF: 0.350 AC: 11715 AN: 33470

American (AMR) AF: 0.116 AC: 5194 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0855 AC: 2235 AN: 26134

East Asian (EAS) AF: 0.260 AC: 10335 AN: 39700

South Asian (SAS) AF: 0.171 AC: 14751 AN: 86254

European-Finnish (FIN) AF: 0.0559 AC: 2987 AN: 53420

Middle Eastern (MID) AF: 0.120 AC: 694 AN: 5762

European-Non Finnish (NFE) AF: 0.0871 AC: 96885 AN: 1111862

Other (OTH) AF: 0.121 AC: 7331 AN: 60382

GnomAD4 genome AF: 0.173 AC: 26414 AN: 152246 Hom.: 3281 Cov.: 33 AF XY: 0.172 AC XY: 12833 AN XY: 74448

African (AFR) AF: 0.348 AC: 14436 AN: 41512

American (AMR) AF: 0.138 AC: 2111 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0847 AC: 294 AN: 3472

East Asian (EAS) AF: 0.256 AC: 1324 AN: 5176

South Asian (SAS) AF: 0.184 AC: 889 AN: 4830

European-Finnish (FIN) AF: 0.0546 AC: 580 AN: 10616

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0924 AC: 6287 AN: 68018

Other (OTH) AF: 0.168 AC: 356 AN: 2114

Alfa AF: 0.134 Hom.: 1124

Bravo AF: 0.185

Asia WGS AF: 0.269 AC: 937 AN: 3478

EpiCase AF: 0.0956

EpiControl AF: 0.0947

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	Norman-Roberts syndrome (3)
-	-	2	not provided (2)
-	-	1	Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.0070
DANN	Benign	0.44
PhyloP100		-2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Mutation Taster		=86/14	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1062831; hg19: chr7-103124207; COSMIC: COSV59004479; COSMIC: COSV59004479;