NM_005045.4:c.8667+45T>C

Variant names:

• chr7-103500700-A-G
• rs13232021
• NM_005045.4:c.8667+45T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005045.4(RELN):​c.8667+45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,599,828 control chromosomes in the GnomAD database, including 23,417 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1895 hom., cov: 33)
  • Exomes 𝑓: 0.17 (21522 hom.)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.140
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-103500700-A-G is Benign according to our data. Variant chr7-103500700-A-G is described in ClinVar as Benign. ClinVar VariationId is 259615.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.279 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.8667+45T>C		intron	N/A	NP_005036.2
	RELN	NM_173054.3		c.8667+45T>C		intron	N/A	NP_774959.1
	SLC26A5-AS1	NR_110141.1		n.1366-3704A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELN	ENST00000428762.6	TSL:5 MANE Select	c.8667+45T>C		intron	N/A	ENSP00000392423.1
	SLC26A5-AS1	ENST00000422488.1	TSL:1	n.1366-3704A>G		intron	N/A
	RELN	ENST00000424685.3	TSL:5	c.8667+45T>C		intron	N/A	ENSP00000388446.3

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22544 AN: 152082 Hom.: 1898 Cov.: 33

Gnomad AFR AF: 0.0854

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.142

GnomAD2 exomes AF: 0.180 AC: 44885 AN: 249134 AF XY: 0.184

Gnomad AFR exome AF: 0.0825

Gnomad AMR exome AF: 0.178

Gnomad ASJ exome AF: 0.141

Gnomad EAS exome AF: 0.286

Gnomad FIN exome AF: 0.216

Gnomad NFE exome AF: 0.154

Gnomad OTH exome AF: 0.177

GnomAD4 exome AF: 0.166 AC: 239860 AN: 1447628 Hom.: 21522 Cov.: 28 AF XY: 0.169 AC XY: 121319 AN XY: 719980

African (AFR) AF: 0.0808 AC: 2679 AN: 33154

American (AMR) AF: 0.175 AC: 7785 AN: 44464

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 3630 AN: 25962

East Asian (EAS) AF: 0.332 AC: 13126 AN: 39570

South Asian (SAS) AF: 0.255 AC: 21883 AN: 85734

European-Finnish (FIN) AF: 0.211 AC: 11263 AN: 53344

Middle Eastern (MID) AF: 0.122 AC: 585 AN: 4784

European-Non Finnish (NFE) AF: 0.153 AC: 168941 AN: 1100866

Other (OTH) AF: 0.167 AC: 9968 AN: 59750

GnomAD4 genome AF: 0.148 AC: 22551 AN: 152200 Hom.: 1895 Cov.: 33 AF XY: 0.156 AC XY: 11572 AN XY: 74406

African (AFR) AF: 0.0853 AC: 3544 AN: 41556

American (AMR) AF: 0.156 AC: 2382 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 468 AN: 3468

East Asian (EAS) AF: 0.292 AC: 1507 AN: 5166

South Asian (SAS) AF: 0.268 AC: 1294 AN: 4822

European-Finnish (FIN) AF: 0.218 AC: 2307 AN: 10592

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10572 AN: 68004

Other (OTH) AF: 0.141 AC: 298 AN: 2114

Alfa AF: 0.152 Hom.: 7161

Bravo AF: 0.138

Asia WGS AF: 0.265 AC: 920 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.5
DANN	Benign	0.42
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs13232021; hg19: chr7-103141147; COSMIC: COSV58991965;