NM_005045.4:c.*151T>C

Variant names:

• chr7-103472661-A-G
• rs7811571
• NM_005045.4:c.*151T>C

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.*151T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 665,552 control chromosomes in the GnomAD database, including 610 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (427 hom., cov: 32)
  • Exomes 𝑓: 0.0054 (183 hom.)
• Consequence: RELN NM_005045.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.34
• 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=-0.36).
• BP6: Variant 7-103472661-A-G is Benign according to our data. Variant chr7-103472661-A-G is described in ClinVar as [Benign]. Clinvar id is 358370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RELN	NM_005045.4	c.*151T>C		3_prime_UTR_variant	Exon 65 of 65	ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.*151T>C		3_prime_UTR_variant	Exon 64 of 64		NP_774959.1
SLC26A5-AS1	NR_110141.1	n.1365+25993A>G		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.*151T>C		3_prime_UTR_variant	Exon 65 of 65	5	NM_005045.4	ENSP00000392423.1

Frequencies

GnomAD3 genomes AF: 0.0412 AC: 6272 AN: 152150 Hom.: 423 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.0330

GnomAD4 exome AF: 0.00538 AC: 2762 AN: 513284 Hom.: 183 Cov.: 5 AF XY: 0.00439 AC XY: 1206 AN XY: 274414

African (AFR) AF: 0.150 AC: 2118 AN: 14140

American (AMR) AF: 0.00725 AC: 212 AN: 29224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16806

East Asian (EAS) AF: 0.00 AC: 0 AN: 31064

South Asian (SAS) AF: 0.000376 AC: 20 AN: 53174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40388

Middle Eastern (MID) AF: 0.00749 AC: 17 AN: 2270

European-Non Finnish (NFE) AF: 0.000268 AC: 80 AN: 298048

Other (OTH) AF: 0.0112 AC: 315 AN: 28170

GnomAD4 genome AF: 0.0414 AC: 6300 AN: 152268 Hom.: 427 Cov.: 32 AF XY: 0.0404 AC XY: 3005 AN XY: 74454

African (AFR) AF: 0.144 AC: 5979 AN: 41524

American (AMR) AF: 0.0141 AC: 215 AN: 15300

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.000529 AC: 36 AN: 68022

Other (OTH) AF: 0.0327 AC: 69 AN: 2112

Alfa AF: 0.0174 Hom.: 194

Bravo AF: 0.0474

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Norman-Roberts syndrome Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	8.1
DANN	Benign	0.73
PhyloP100		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7811571; hg19: chr7-103113108;