chr7-103472730-A-G

Variant names:

• chr7-103472730-A-G
• rs781050842
• NM_005045.4:c.*82T>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BS1_Supporting BS2

The NM_005045.4(RELN):​c.*82T>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00101 in 1,094,852 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00079 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (11 hom.)
• Consequence: RELN NM_005045.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.42
• 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000788 (120/152318) while in subpopulation SAS AF = 0.000828 (4/4830). AF 95% confidence interval is 0.000282. There are 1 homozygotes in GnomAd4. There are 50 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAdExome4 at 11 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.*82T>C		3_prime_UTR	Exon 65 of 65	NP_005036.2
	RELN	NM_173054.3		c.*82T>C		3_prime_UTR	Exon 64 of 64	NP_774959.1	P78509-2
	SLC26A5-AS1	NR_110141.1		n.1365+26062A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELN	ENST00000428762.6	TSL:5 MANE Select	c.*82T>C		3_prime_UTR	Exon 65 of 65	ENSP00000392423.1	P78509-1
	SLC26A5-AS1	ENST00000422488.1	TSL:1	n.1365+26062A>G		intron	N/A
	RELN	ENST00000424685.3	TSL:5	c.*185T>C		3_prime_UTR	Exon 65 of 65	ENSP00000388446.3	J3KQ66

Frequencies

GnomAD3 genomes AF: 0.000788 AC: 120 AN: 152200 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.000956

GnomAD4 exome AF: 0.00104 AC: 983 AN: 942534 Hom.: 11 Cov.: 12 AF XY: 0.00105 AC XY: 513 AN XY: 488642

African (AFR) AF: 0.00 AC: 0 AN: 23194

American (AMR) AF: 0.00 AC: 0 AN: 39916

Ashkenazi Jewish (ASJ) AF: 0.0323 AC: 731 AN: 22612

East Asian (EAS) AF: 0.00 AC: 0 AN: 36302

South Asian (SAS) AF: 0.000191 AC: 14 AN: 73130

European-Finnish (FIN) AF: 0.0000195 AC: 1 AN: 51354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4512

European-Non Finnish (NFE) AF: 0.000197 AC: 128 AN: 648360

Other (OTH) AF: 0.00253 AC: 109 AN: 43154

GnomAD4 genome AF: 0.000788 AC: 120 AN: 152318 Hom.: 1 Cov.: 32 AF XY: 0.000671 AC XY: 50 AN XY: 74476

African (AFR) AF: 0.0000481 AC: 2 AN: 41580

American (AMR) AF: 0.0000654 AC: 1 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0280 AC: 97 AN: 3468

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

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68022

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.0000695 Hom.: 0

Bravo AF: 0.000914

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Norman-Roberts syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	14
DANN	Benign	0.89
PhyloP100		6.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs781050842; hg19: chr7-103113177;