rs7811262

Variant names:

• chr7-103472415-C-T
• rs7811262
• NM_005045.4:c.*397G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-103472415-C-T
• chr7-103472415-C-A
• chr7-103472415-C-G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_005045.4(RELN):​c.*397G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.992 in 256,042 control chromosomes in the GnomAD database, including 126,082 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.99 (75099 hom., cov: 33)
  • Exomes 𝑓: 0.99 (50983 hom.)
• Consequence: RELN NM_005045.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.91
• Publications: 3 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 7-103472415-C-T is Benign according to our data. Variant chr7-103472415-C-T is described in ClinVar as Benign. ClinVar VariationId is 358369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 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.*397G>A		3_prime_UTR	Exon 65 of 65	NP_005036.2
	RELN	NM_173054.3		c.*397G>A		3_prime_UTR	Exon 64 of 64	NP_774959.1	P78509-2
	SLC26A5-AS1	NR_110141.1		n.1365+25747C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELN	ENST00000428762.6	TSL:5 MANE Select	c.*397G>A		3_prime_UTR	Exon 65 of 65	ENSP00000392423.1	P78509-1
	SLC26A5-AS1	ENST00000422488.1	TSL:1	n.1365+25747C>T		intron	N/A
	RELN	ENST00000424685.3	TSL:5	c.*500G>A		3_prime_UTR	Exon 65 of 65	ENSP00000388446.3	J3KQ66

Frequencies

GnomAD3 genomes AF: 0.993 AC: 151121 AN: 152180 Hom.: 75040 Cov.: 33

Gnomad AFR AF: 0.998

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.997

Gnomad ASJ AF: 0.998

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 0.977

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.990

Gnomad OTH AF: 0.996

GnomAD4 exome AF: 0.991 AC: 102850 AN: 103744 Hom.: 50983 Cov.: 0 AF XY: 0.992 AC XY: 54377 AN XY: 54802

African (AFR) AF: 0.998 AC: 2586 AN: 2590

American (AMR) AF: 0.999 AC: 4267 AN: 4272

Ashkenazi Jewish (ASJ) AF: 0.998 AC: 2496 AN: 2500

East Asian (EAS) AF: 1.00 AC: 4790 AN: 4790

South Asian (SAS) AF: 0.999 AC: 15805 AN: 15816

European-Finnish (FIN) AF: 0.973 AC: 5094 AN: 5238

Middle Eastern (MID) AF: 1.00 AC: 386 AN: 386

European-Non Finnish (NFE) AF: 0.990 AC: 62093 AN: 62750

Other (OTH) AF: 0.987 AC: 5333 AN: 5402

GnomAD4 genome AF: 0.993 AC: 151239 AN: 152298 Hom.: 75099 Cov.: 33 AF XY: 0.993 AC XY: 73953 AN XY: 74458

African (AFR) AF: 0.998 AC: 41494 AN: 41570

American (AMR) AF: 0.997 AC: 15250 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.998 AC: 3465 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5182 AN: 5182

South Asian (SAS) AF: 1.00 AC: 4825 AN: 4826

European-Finnish (FIN) AF: 0.977 AC: 10368 AN: 10612

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.990 AC: 67345 AN: 68018

Other (OTH) AF: 0.996 AC: 2108 AN: 2116

Alfa AF: 0.992 Hom.: 16092

Bravo AF: 0.995

Asia WGS AF: 0.999 AC: 3473 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Norman-Roberts syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Benign	0.86
PhyloP100		2.9
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: rs7811262; hg19: chr7-103112862;