7-103492056-G-C

Variant names:

• chr7-103492056-G-C
• rs79193208
• NM_005045.4:c.9370-30C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005045.4(RELN):​c.9370-30C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0021 in 1,521,998 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (27 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (24 hom.)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.616
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 7-103492056-G-C is Benign according to our data. Variant chr7-103492056-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 259618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0111 (1682/152102) while in subpopulation AFR AF = 0.0386 (1602/41474). AF 95% confidence interval is 0.0371. There are 27 homozygotes in GnomAd4. There are 810 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 AR,AD gene

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.9370-30C>G		intron	N/A	NP_005036.2
	RELN	NM_173054.3		c.9370-30C>G		intron	N/A	NP_774959.1	P78509-2
	SLC26A5-AS1	NR_110141.1		n.1366-12348G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELN	ENST00000428762.6	TSL:5 MANE Select	c.9370-30C>G		intron	N/A	ENSP00000392423.1	P78509-1
	SLC26A5-AS1	ENST00000422488.1	TSL:1	n.1366-12348G>C		intron	N/A
	RELN	ENST00000424685.3	TSL:5	c.9370-30C>G		intron	N/A	ENSP00000388446.3	J3KQ66

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1679 AN: 151984 Hom.: 28 Cov.: 32

Gnomad AFR AF: 0.0387

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00354

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00277 AC: 659 AN: 237668 AF XY: 0.00205

Gnomad AFR exome AF: 0.0402

Gnomad AMR exome AF: 0.00144

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000282

Gnomad OTH exome AF: 0.00102

GnomAD4 exome AF: 0.00110 AC: 1511 AN: 1369896 Hom.: 24 Cov.: 22 AF XY: 0.000958 AC XY: 657 AN XY: 685744

African (AFR) AF: 0.0401 AC: 1270 AN: 31668

American (AMR) AF: 0.00183 AC: 80 AN: 43778

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25334

East Asian (EAS) AF: 0.00 AC: 0 AN: 39118

South Asian (SAS) AF: 0.000108 AC: 9 AN: 83138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52898

Middle Eastern (MID) AF: 0.00125 AC: 7 AN: 5580

European-Non Finnish (NFE) AF: 0.00000970 AC: 10 AN: 1030996

Other (OTH) AF: 0.00235 AC: 135 AN: 57386

GnomAD4 genome AF: 0.0111 AC: 1682 AN: 152102 Hom.: 27 Cov.: 32 AF XY: 0.0109 AC XY: 810 AN XY: 74348

African (AFR) AF: 0.0386 AC: 1602 AN: 41474

American (AMR) AF: 0.00353 AC: 54 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67996

Other (OTH) AF: 0.0104 AC: 22 AN: 2112

Alfa AF: 0.00632 Hom.: 3

Bravo AF: 0.0125

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.4
DANN	Benign	0.53
PhyloP100		0.62
Mutation Taster		=100/0	polymorphism

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: rs79193208; hg19: chr7-103132503;