4-7323275-T-C

Variant names:

• chr4-7323275-T-C
• rs4689705
• NM_020777.3:c.481-73013T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020777.3(SORCS2):​c.481-73013T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 152,140 control chromosomes in the GnomAD database, including 46,465 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 0.78 (46465 hom., cov: 32)
• Consequence: SORCS2 NM_020777.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020777.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORCS2	NM_020777.3	MANE Select	c.481-73013T>C		intron	N/A	NP_065828.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORCS2	ENST00000507866.6	TSL:1 MANE Select	c.481-73013T>C		intron	N/A	ENSP00000422185.2

Frequencies

GnomAD3 genomes AF: 0.776 AC: 117903 AN: 152022 Hom.: 46405 Cov.: 32

Gnomad AFR AF: 0.916

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.745

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.784

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

GnomAD4 genome AF: 0.776 AC: 118022 AN: 152140 Hom.: 46465 Cov.: 32 AF XY: 0.774 AC XY: 57575 AN XY: 74350

African (AFR) AF: 0.916 AC: 38069 AN: 41542

American (AMR) AF: 0.786 AC: 12019 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2558 AN: 3470

East Asian (EAS) AF: 0.827 AC: 4273 AN: 5164

South Asian (SAS) AF: 0.598 AC: 2881 AN: 4814

European-Finnish (FIN) AF: 0.721 AC: 7632 AN: 10578

Middle Eastern (MID) AF: 0.747 AC: 218 AN: 292

European-Non Finnish (NFE) AF: 0.706 AC: 47991 AN: 67970

Other (OTH) AF: 0.787 AC: 1660 AN: 2108

Alfa AF: 0.719 Hom.: 74114

Bravo AF: 0.787

Asia WGS AF: 0.755 AC: 2628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.5
DANN	Benign	0.45
PhyloP100		-1.2
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: rs4689705; hg19: chr4-7325002; COSMIC: COSV72724113;