7-103489956-A-G

Variant names:

• chr7-103489956-A-G
• rs736707
• NM_005045.4:c.9606-57T>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.9606-57T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 1,602,426 control chromosomes in the GnomAD database, including 50,574 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7625 hom., cov: 32)
  • Exomes 𝑓: 0.23 (42949 hom.)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.46
• Publications: 43 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=-0.96).
• BP6: Variant 7-103489956-A-G is Benign according to our data. Variant chr7-103489956-A-G is described in ClinVar as Benign. ClinVar VariationId is 1295479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RELN	NM_005045.4	c.9606-57T>C		intron_variant	Intron 59 of 64	ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.9606-57T>C		intron_variant	Intron 59 of 63		NP_774959.1
SLC26A5-AS1	NR_110141.1	n.1366-14448A>G		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.9606-57T>C		intron_variant	Intron 59 of 64	5	NM_005045.4	ENSP00000392423.1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44880 AN: 151858 Hom.: 7624 Cov.: 32

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.276

GnomAD4 exome AF: 0.232 AC: 337181 AN: 1450450 Hom.: 42949 AF XY: 0.236 AC XY: 170094 AN XY: 721946

African (AFR) AF: 0.466 AC: 15538 AN: 33318

American (AMR) AF: 0.221 AC: 9829 AN: 44452

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 5345 AN: 26064

East Asian (EAS) AF: 0.491 AC: 19439 AN: 39582

South Asian (SAS) AF: 0.352 AC: 30154 AN: 85550

European-Finnish (FIN) AF: 0.240 AC: 12248 AN: 51116

Middle Eastern (MID) AF: 0.207 AC: 1172 AN: 5664

European-Non Finnish (NFE) AF: 0.207 AC: 228415 AN: 1104658

Other (OTH) AF: 0.250 AC: 15041 AN: 60046

GnomAD4 genome AF: 0.296 AC: 44922 AN: 151976 Hom.: 7625 Cov.: 32 AF XY: 0.298 AC XY: 22172 AN XY: 74310

African (AFR) AF: 0.458 AC: 18970 AN: 41428

American (AMR) AF: 0.222 AC: 3386 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 703 AN: 3468

East Asian (EAS) AF: 0.455 AC: 2343 AN: 5146

South Asian (SAS) AF: 0.366 AC: 1754 AN: 4798

European-Finnish (FIN) AF: 0.246 AC: 2602 AN: 10584

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14341 AN: 67960

Other (OTH) AF: 0.275 AC: 580 AN: 2110

Alfa AF: 0.236 Hom.: 20346

Bravo AF: 0.298

Asia WGS AF: 0.413 AC: 1436 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0030
DANN	Benign	0.26
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs736707; hg19: chr7-103130403; COSMIC: COSV58991874; COSMIC: COSV58991874;