rs2229862

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr7-103500904-G-A
• chr7-103500904-G-C

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_005045.4(RELN):​c.8508C>T​(p.Phe2836Phe) variant causes a synonymous change. The variant allele was found at a frequency of 0.0467 in 1,613,868 control chromosomes in the GnomAD database, including 1,932 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (137 hom., cov: 32)
  • Exomes 𝑓: 0.048 (1795 hom.)
• Consequence: RELN NM_005045.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• 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: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 7-103500904-G-A is Benign according to our data. Variant chr7-103500904-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 95233.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0525 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELN	NM_005045.4	MANE Select	c.8508C>T	p.Phe2836Phe	synonymous	Exon 53 of 65	NP_005036.2
	RELN	NM_173054.3		c.8508C>T	p.Phe2836Phe	synonymous	Exon 53 of 64	NP_774959.1	P78509-2
	SLC26A5-AS1	NR_110141.1		n.1366-3500G>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.8508C>T	p.Phe2836Phe	synonymous	Exon 53 of 65	ENSP00000392423.1	P78509-1
	SLC26A5-AS1	ENST00000422488.1	TSL:1	n.1366-3500G>A		intron	N/A
	RELN	ENST00000424685.3	TSL:5	c.8508C>T	p.Phe2836Phe	synonymous	Exon 53 of 65	ENSP00000388446.3	J3KQ66

Frequencies

GnomAD3 genomes AF: 0.0368 AC: 5595 AN: 152126 Hom.: 137 Cov.: 32

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0488

Gnomad ASJ AF: 0.0352

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.0449

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0539

Gnomad OTH AF: 0.0368

GnomAD2 exomes AF: 0.0361 AC: 9066 AN: 251314 AF XY: 0.0369

Gnomad AFR exome AF: 0.00855

Gnomad AMR exome AF: 0.0275

Gnomad ASJ exome AF: 0.0363

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0492

Gnomad NFE exome AF: 0.0513

Gnomad OTH exome AF: 0.0486

GnomAD4 exome AF: 0.0477 AC: 69699 AN: 1461624 Hom.: 1795 Cov.: 32 AF XY: 0.0466 AC XY: 33865 AN XY: 727120

African (AFR) AF: 0.00789 AC: 264 AN: 33472

American (AMR) AF: 0.0288 AC: 1286 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0367 AC: 959 AN: 26130

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39698

South Asian (SAS) AF: 0.0144 AC: 1239 AN: 86240

European-Finnish (FIN) AF: 0.0514 AC: 2744 AN: 53418

Middle Eastern (MID) AF: 0.0135 AC: 78 AN: 5766

European-Non Finnish (NFE) AF: 0.0545 AC: 60569 AN: 1111792

Other (OTH) AF: 0.0423 AC: 2554 AN: 60388

GnomAD4 genome AF: 0.0368 AC: 5595 AN: 152244 Hom.: 137 Cov.: 32 AF XY: 0.0367 AC XY: 2732 AN XY: 74438

African (AFR) AF: 0.0101 AC: 421 AN: 41556

American (AMR) AF: 0.0487 AC: 745 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0352 AC: 122 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.0168 AC: 81 AN: 4822

European-Finnish (FIN) AF: 0.0449 AC: 475 AN: 10590

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0539 AC: 3668 AN: 68022

Other (OTH) AF: 0.0365 AC: 77 AN: 2112

Alfa AF: 0.0421 Hom.: 164

Bravo AF: 0.0350

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.0502

EpiControl AF: 0.0493

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	2	not provided (2)
-	-	1	Norman-Roberts syndrome (1)
-	-	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	-0.33
CADD	Benign	9.2
DANN	Benign	0.83
PhyloP100		4.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2229862; hg19: chr7-103141351; COSMIC: COSV59033924;