7-103989356-TGCCGCCGCCGCCGCC-TGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCC

Variant names:

• chr7-103989356-T-TGCCGCCGCCGCCGCCGCCGCCGCCGCCGCC
• rs55656324
• NM_005045.4:c.-1_1insGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_005045.4(RELN):​c.-1_1insGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000087 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RELN NM_005045.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000135 (20/148368) while in subpopulation EAS AF= 0.00106 (5/4698). AF 95% confidence interval is 0.000419. There are 0 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RELN	NM_005045.4	c.-1_1insGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 65	ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.-1_1insGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 64		NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.-1_1insGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 65	5	NM_005045.4	ENSP00000392423.1

Frequencies

GnomAD3 genomes AF: 0.000142 AC: 21 AN: 148270 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000323

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000665

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00106

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000994

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000150

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000873 AC: 11 AN: 1259862 Hom.: 0 Cov.: 36 AF XY: 0.00000645 AC XY: 4 AN XY: 620584

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000738

Gnomad4 SAS exome AF: 0.0000533

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000394

Gnomad4 OTH exome AF: 0.0000384

GnomAD4 genome AF: 0.000135 AC: 20 AN: 148368 Hom.: 0 Cov.: 0 AF XY: 0.000111 AC XY: 8 AN XY: 72354

Gnomad4 AFR AF: 0.000298

Gnomad4 AMR AF: 0.0000665

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00106

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000994

Gnomad4 NFE AF: 0.0000150

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs55656324; hg19: chr7-103629803;