chr7-103472415-C-T

Position:

• chr7-103472415-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELN	NM_005045.4	c.*397G>A		3_prime_UTR_variant	65/65	ENST00000428762.6	NP_005036.2
SLC26A5-AS1	NR_110141.1	n.1365+25747C>T		intron_variant, non_coding_transcript_variant
RELN	NM_173054.3	c.*397G>A		3_prime_UTR_variant	64/64		NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.*397G>A		3_prime_UTR_variant	65/65	5	NM_005045.4	ENSP00000392423	P5
SLC26A5-AS1	ENST00000422488.1	n.1365+25747C>T		intron_variant, non_coding_transcript_variant		1

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

Gnomad4 AFR exome AF: 0.998

Gnomad4 AMR exome AF: 0.999

Gnomad4 ASJ exome AF: 0.998

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.999

Gnomad4 FIN exome AF: 0.973

Gnomad4 NFE exome AF: 0.990

Gnomad4 OTH exome AF: 0.987

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

Gnomad4 AFR AF: 0.998

Gnomad4 AMR AF: 0.997

Gnomad4 ASJ AF: 0.998

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 0.977

Gnomad4 NFE AF: 0.990

Gnomad4 OTH AF: 0.996

Alfa AF: 0.991 Hom.: 13797

Bravo AF: 0.995

Asia WGS AF: 0.999 AC: 3473 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Norman-Roberts syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs7811262; hg19: chr7-103112862;