chr4-7426104-T-C

Variant names:

• chr4-7426104-T-C
• rs11733360
• NM_020777.3:c.548+29749T>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.548+29749T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,206 control chromosomes in the GnomAD database, including 3,612 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 0.20 (3612 hom., cov: 33)
• Consequence: SORCS2 NM_020777.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19
• Publications: 1 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS2	NM_020777.3	c.548+29749T>C		intron_variant	Intron 2 of 26	ENST00000507866.6	NP_065828.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORCS2	ENST00000507866.6	c.548+29749T>C		intron_variant	Intron 2 of 26	1	NM_020777.3	ENSP00000422185.2
SORCS2	ENST00000511199.1	n.163+29749T>C		intron_variant	Intron 2 of 5	4

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30444 AN: 152088 Hom.: 3613 Cov.: 33

Gnomad AFR AF: 0.0924

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.200 AC: 30440 AN: 152206 Hom.: 3612 Cov.: 33 AF XY: 0.197 AC XY: 14628 AN XY: 74434

African (AFR) AF: 0.0923 AC: 3835 AN: 41544

American (AMR) AF: 0.204 AC: 3127 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1250 AN: 3470

East Asian (EAS) AF: 0.130 AC: 672 AN: 5166

South Asian (SAS) AF: 0.188 AC: 905 AN: 4816

European-Finnish (FIN) AF: 0.200 AC: 2126 AN: 10612

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.259 AC: 17606 AN: 67988

Other (OTH) AF: 0.231 AC: 488 AN: 2114

Alfa AF: 0.238 Hom.: 3693

Bravo AF: 0.197

Asia WGS AF: 0.161 AC: 562 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.080
DANN	Benign	0.36
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11733360; hg19: chr4-7427831;