chr7-103492033-CAAACAT-C

Variant names:

• chr7-103492033-CAAACAT-C
• rs141397961
• NM_005045.4:c.9370-13_9370-8delATGTTT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_005045.4(RELN):​c.9370-13_9370-8delATGTTT variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00291 in 1,605,952 control chromosomes in the GnomAD database, including 113 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (56 hom., cov: 31)
  • Exomes 𝑓: 0.0016 (57 hom.)
• Consequence: RELN NM_005045.4 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 5.08
• Publications: 0 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 -16 ACMG points.

• BP6: Variant 7-103492033-CAAACAT-C is Benign according to our data. Variant chr7-103492033-CAAACAT-C is described in ClinVar as Benign. ClinVar VariationId is 95238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0512 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.9370-13_9370-8delATGTTT		splice_region intron	N/A	NP_005036.2
	RELN	NM_173054.3		c.9370-13_9370-8delATGTTT		splice_region intron	N/A	NP_774959.1	P78509-2
	SLC26A5-AS1	NR_110141.1		n.1366-12365_1366-12360delTAAACA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELN	ENST00000428762.6	TSL:5 MANE Select	c.9370-13_9370-8delATGTTT		splice_region intron	N/A	ENSP00000392423.1	P78509-1
	SLC26A5-AS1	ENST00000422488.1	TSL:1	n.1366-12370_1366-12365delAAACAT		intron	N/A
	RELN	ENST00000424685.3	TSL:5	c.9370-13_9370-8delATGTTT		splice_region intron	N/A	ENSP00000388446.3	J3KQ66

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2283 AN: 152020 Hom.: 56 Cov.: 31

Gnomad AFR AF: 0.0512

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00740

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.00908

GnomAD2 exomes AF: 0.00394 AC: 976 AN: 247494 AF XY: 0.00299

Gnomad AFR exome AF: 0.0523

Gnomad AMR exome AF: 0.00324

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000223

Gnomad OTH exome AF: 0.00198

GnomAD4 exome AF: 0.00164 AC: 2379 AN: 1453814 Hom.: 57 AF XY: 0.00135 AC XY: 978 AN XY: 723450

African (AFR) AF: 0.0533 AC: 1774 AN: 33306

American (AMR) AF: 0.00407 AC: 181 AN: 44494

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25980

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.000140 AC: 12 AN: 85634

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53306

Middle Eastern (MID) AF: 0.00278 AC: 16 AN: 5758

European-Non Finnish (NFE) AF: 0.000150 AC: 166 AN: 1105590

Other (OTH) AF: 0.00383 AC: 230 AN: 60122

GnomAD4 genome AF: 0.0150 AC: 2288 AN: 152138 Hom.: 56 Cov.: 31 AF XY: 0.0147 AC XY: 1093 AN XY: 74386

African (AFR) AF: 0.0512 AC: 2124 AN: 41482

American (AMR) AF: 0.00739 AC: 113 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 67990

Other (OTH) AF: 0.00899 AC: 19 AN: 2114

Alfa AF: 0.00740 Hom.: 3

Bravo AF: 0.0176

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7 (1)
-	-	1	not provided (1)
-	-	1	RELN-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.1
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs141397961; hg19: chr7-103132480;