rs6814708

Variant names:

• chr4-7278597-T-C
• rs6814708
• NM_020777.3:c.480+85471T>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.480+85471T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 152,024 control chromosomes in the GnomAD database, including 10,423 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 0.36 (10423 hom., cov: 32)
• Consequence: SORCS2 NM_020777.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.406 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORCS2	NM_020777.3	MANE Select	c.480+85471T>C		intron	N/A	NP_065828.2	Q96PQ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORCS2	ENST00000507866.6	TSL:1 MANE Select	c.480+85471T>C		intron	N/A	ENSP00000422185.2	Q96PQ0

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54791 AN: 151906 Hom.: 10412 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.0613

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.379

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

GnomAD4 genome AF: 0.361 AC: 54835 AN: 152024 Hom.: 10423 Cov.: 32 AF XY: 0.352 AC XY: 26181 AN XY: 74286

African (AFR) AF: 0.411 AC: 17030 AN: 41458

American (AMR) AF: 0.294 AC: 4495 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 816 AN: 3470

East Asian (EAS) AF: 0.0614 AC: 317 AN: 5160

South Asian (SAS) AF: 0.170 AC: 822 AN: 4828

European-Finnish (FIN) AF: 0.372 AC: 3934 AN: 10562

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.385 AC: 26184 AN: 67956

Other (OTH) AF: 0.377 AC: 793 AN: 2104

Alfa AF: 0.364 Hom.: 29905

Bravo AF: 0.357

Asia WGS AF: 0.150 AC: 525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.57
DANN	Benign	0.79
PhyloP100		-0.27
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: rs6814708; hg19: chr4-7280324;