NM_005045.4:c.8843+7G>C

Variant names:

• chr7-103498070-C-G
• rs2711885
• NM_005045.4:c.8843+7G>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.8843+7G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 1,613,976 control chromosomes in the GnomAD database, including 786,013 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.99 (74597 hom., cov: 32)
  • Exomes 𝑓: 0.99 (711416 hom.)
• Consequence: RELN NM_005045.4 splice_region, intron
• Scores: Splicing: ADA: 0.00001489
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.100
• Publications: 13 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=-0.89).
• BP6: Variant 7-103498070-C-G is Benign according to our data. Variant chr7-103498070-C-G is described in ClinVar as Benign. ClinVar VariationId is 95234.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.989 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.8843+7G>C		splice_region intron	N/A	NP_005036.2
	RELN	NM_173054.3		c.8843+7G>C		splice_region intron	N/A	NP_774959.1	P78509-2
	SLC26A5-AS1	NR_110141.1		n.1366-6334C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELN	ENST00000428762.6	TSL:5 MANE Select	c.8843+7G>C		splice_region intron	N/A	ENSP00000392423.1	P78509-1
	SLC26A5-AS1	ENST00000422488.1	TSL:1	n.1366-6334C>G		intron	N/A
	RELN	ENST00000424685.3	TSL:5	c.8843+7G>C		splice_region intron	N/A	ENSP00000388446.3	J3KQ66

Frequencies

GnomAD3 genomes AF: 0.990 AC: 150621 AN: 152198 Hom.: 74537 Cov.: 32

Gnomad AFR AF: 0.997

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.994

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.992

Gnomad FIN AF: 0.977

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.986

Gnomad OTH AF: 0.988

GnomAD2 exomes AF: 0.987 AC: 247858 AN: 251068 AF XY: 0.987

Gnomad AFR exome AF: 0.998

Gnomad AMR exome AF: 0.995

Gnomad ASJ exome AF: 0.978

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.973

Gnomad NFE exome AF: 0.985

Gnomad OTH exome AF: 0.982

GnomAD4 exome AF: 0.987 AC: 1442059 AN: 1461660 Hom.: 711416 Cov.: 43 AF XY: 0.987 AC XY: 717415 AN XY: 727152

African (AFR) AF: 0.998 AC: 33403 AN: 33472

American (AMR) AF: 0.995 AC: 44467 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 25555 AN: 26134

East Asian (EAS) AF: 1.00 AC: 39692 AN: 39694

South Asian (SAS) AF: 0.990 AC: 85382 AN: 86242

European-Finnish (FIN) AF: 0.971 AC: 51893 AN: 53418

Middle Eastern (MID) AF: 0.981 AC: 5657 AN: 5768

European-Non Finnish (NFE) AF: 0.986 AC: 1096411 AN: 1111834

Other (OTH) AF: 0.987 AC: 59599 AN: 60388

GnomAD4 genome AF: 0.990 AC: 150741 AN: 152316 Hom.: 74597 Cov.: 32 AF XY: 0.990 AC XY: 73739 AN XY: 74486

African (AFR) AF: 0.997 AC: 41448 AN: 41554

American (AMR) AF: 0.994 AC: 15202 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.975 AC: 3384 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5184 AN: 5184

South Asian (SAS) AF: 0.992 AC: 4791 AN: 4828

European-Finnish (FIN) AF: 0.977 AC: 10376 AN: 10624

Middle Eastern (MID) AF: 0.973 AC: 286 AN: 294

European-Non Finnish (NFE) AF: 0.986 AC: 67076 AN: 68036

Other (OTH) AF: 0.988 AC: 2086 AN: 2112

Alfa AF: 0.985 Hom.: 23935

Bravo AF: 0.991

Asia WGS AF: 0.995 AC: 3461 AN: 3478

EpiCase AF: 0.985

EpiControl AF: 0.986

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Norman-Roberts syndrome (3)
-	-	3	not provided (3)
-	-	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	-0.89
CADD	Benign	1.7
DANN	Benign	0.52
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000015
dbscSNV1_RF	Benign	0.0
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: rs2711885; hg19: chr7-103138517;