NM_005045.4:c.7887T>C

Variant names:

• chr7-103515417-A-G
• rs56345626
• NM_005045.4:c.7887T>C

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.7887T>C​(p.Pro2629Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 1,613,810 control chromosomes in the GnomAD database, including 27,618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2305 hom., cov: 32)
  • Exomes 𝑓: 0.18 (25313 hom.)
• Consequence: RELN NM_005045.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.924
• Publications: 15 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=-0.47).
• BP6: Variant 7-103515417-A-G is Benign according to our data. Variant chr7-103515417-A-G is described in ClinVar as Benign. ClinVar VariationId is 130142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.924 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 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.7887T>C	p.Pro2629Pro	synonymous	Exon 50 of 65	NP_005036.2
	RELN	NM_173054.3		c.7887T>C	p.Pro2629Pro	synonymous	Exon 50 of 64	NP_774959.1	P78509-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELN	ENST00000428762.6	TSL:5 MANE Select	c.7887T>C	p.Pro2629Pro	synonymous	Exon 50 of 65	ENSP00000392423.1	P78509-1
	RELN	ENST00000424685.3	TSL:5	c.7887T>C	p.Pro2629Pro	synonymous	Exon 50 of 65	ENSP00000388446.3	J3KQ66
	RELN	ENST00000343529.9	TSL:5	c.7887T>C	p.Pro2629Pro	synonymous	Exon 50 of 64	ENSP00000345694.5	P78509-2

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26230 AN: 152010 Hom.: 2310 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.171

GnomAD2 exomes AF: 0.180 AC: 45156 AN: 250546 AF XY: 0.181

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.146

Gnomad ASJ exome AF: 0.170

Gnomad EAS exome AF: 0.269

Gnomad FIN exome AF: 0.212

Gnomad NFE exome AF: 0.184

Gnomad OTH exome AF: 0.191

GnomAD4 exome AF: 0.183 AC: 268037 AN: 1461682 Hom.: 25313 Cov.: 38 AF XY: 0.183 AC XY: 133367 AN XY: 727124

African (AFR) AF: 0.130 AC: 4365 AN: 33472

American (AMR) AF: 0.148 AC: 6603 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 4435 AN: 26136

East Asian (EAS) AF: 0.290 AC: 11498 AN: 39700

South Asian (SAS) AF: 0.159 AC: 13689 AN: 86246

European-Finnish (FIN) AF: 0.210 AC: 11204 AN: 53350

Middle Eastern (MID) AF: 0.200 AC: 1153 AN: 5768

European-Non Finnish (NFE) AF: 0.183 AC: 203950 AN: 1111904

Other (OTH) AF: 0.184 AC: 11140 AN: 60390

GnomAD4 genome AF: 0.172 AC: 26235 AN: 152128 Hom.: 2305 Cov.: 32 AF XY: 0.174 AC XY: 12909 AN XY: 74368

African (AFR) AF: 0.132 AC: 5472 AN: 41520

American (AMR) AF: 0.158 AC: 2420 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 588 AN: 3468

East Asian (EAS) AF: 0.268 AC: 1380 AN: 5156

South Asian (SAS) AF: 0.164 AC: 789 AN: 4822

European-Finnish (FIN) AF: 0.214 AC: 2262 AN: 10584

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12747 AN: 67972

Other (OTH) AF: 0.169 AC: 357 AN: 2114

Alfa AF: 0.175 Hom.: 1422

Bravo AF: 0.167

Asia WGS AF: 0.199 AC: 693 AN: 3478

EpiCase AF: 0.188

EpiControl AF: 0.183

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	not provided (3)
-	-	2	Norman-Roberts syndrome (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	-0.47
CADD	Benign	7.7
DANN	Benign	0.74
PhyloP100		0.92
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: rs56345626; hg19: chr7-103155864; COSMIC: COSV59000939; COSMIC: COSV59000939;