rs4484302

chr4-7435270-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020777.3(SORCS2):c.548+38915C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 151,988 control chromosomes in the GnomAD database, including 52,757 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.83 (52757 hom., cov: 31)
• Consequence: SORCS2 NM_020777.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344

Genes affected

SORCS2 (HGNC:16698): (sortilin related VPS10 domain containing receptor 2) This gene encodes one family member of vacuolar protein sorting 10 (VPS10) domain-containing receptor proteins. The VPS10 domain name comes from the yeast carboxypeptidase Y sorting receptor Vps10 protein. Members of this gene family are large with many exons but the CDS lengths are usually less than 3700 nt. Very large introns typically separate the exons encoding the VPS10 domain; the remaining exons are separated by much smaller-sized introns. These genes are strongly expressed in the central nervous system. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORCS2	NM_020777.3	c.548+38915C>T		intron_variant		ENST00000507866.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORCS2	ENST00000507866.6	c.548+38915C>T		intron_variant		1	NM_020777.3	P1
SORCS2	ENST00000511199.1	n.163+38915C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126503 AN: 151870 Hom.: 52733 Cov.: 31

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.883

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.888

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.955

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.847

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.833 AC: 126583 AN: 151988 Hom.: 52757 Cov.: 31 AF XY: 0.835 AC XY: 62068 AN XY: 74292

Gnomad4 AFR AF: 0.801

Gnomad4 AMR AF: 0.851

Gnomad4 ASJ AF: 0.888

Gnomad4 EAS AF: 0.904

Gnomad4 SAS AF: 0.955

Gnomad4 FIN AF: 0.832

Gnomad4 NFE AF: 0.830

Gnomad4 OTH AF: 0.849

Alfa AF: 0.823 Hom.: 6396

Bravo AF: 0.833

Asia WGS AF: 0.921 AC: 3205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.6
Dann	Benign	0.61

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: rs4484302; hg19: chr4-7436997;