rs17585355

Variant names:

• chr1-109315193-A-C
• rs17585355
• NM_002959.7:c.2251-415T>G

Variant summary

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

The NM_002959.7(SORT1):​c.2251-415T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0387 in 152,322 control chromosomes in the GnomAD database, including 183 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 0.039 (183 hom., cov: 31)
• Consequence: SORT1 NM_002959.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390
• Publications: 9 publications found

Genes affected

SORT1 (HGNC:11186): (sortilin 1) This gene encodes a member of the VPS10-related sortilin family of proteins. The encoded preproprotein is proteolytically processed by furin to generate the mature receptor. This receptor plays a role in the trafficking of different proteins to either the cell surface, or subcellular compartments such as lysosomes and endosomes. Expression levels of this gene may influence the risk of myocardial infarction in human patients. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

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 (NFE) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002959.7. 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
	SORT1	NM_002959.7	MANE Select	c.2251-415T>G		intron	N/A	NP_002950.3
	SORT1	NM_001205228.2		c.1840-415T>G		intron	N/A	NP_001192157.1	Q99523-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORT1	ENST00000256637.8	TSL:1 MANE Select	c.2251-415T>G		intron	N/A	ENSP00000256637.6	Q99523-1
	SORT1	ENST00000902724.1		c.2368-415T>G		intron	N/A	ENSP00000572783.1
	SORT1	ENST00000957898.1		c.2365-415T>G		intron	N/A	ENSP00000627957.1

Frequencies

GnomAD3 genomes AF: 0.0388 AC: 5901 AN: 152204 Hom.: 183 Cov.: 31

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0226

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.0754

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0583

Gnomad OTH AF: 0.0311

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

GnomAD4 genome AF: 0.0387 AC: 5898 AN: 152322 Hom.: 183 Cov.: 31 AF XY: 0.0389 AC XY: 2899 AN XY: 74484

African (AFR) AF: 0.0110 AC: 458 AN: 41572

American (AMR) AF: 0.0226 AC: 346 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 57 AN: 3470

East Asian (EAS) AF: 0.000963 AC: 5 AN: 5190

South Asian (SAS) AF: 0.0174 AC: 84 AN: 4826

European-Finnish (FIN) AF: 0.0754 AC: 800 AN: 10610

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0583 AC: 3968 AN: 68024

Other (OTH) AF: 0.0307 AC: 65 AN: 2114

Alfa AF: 0.0393 Hom.: 94

Bravo AF: 0.0341

Asia WGS AF: 0.00837 AC: 29 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	6.1
DANN	Benign	0.72
PhyloP100		-0.039
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: rs17585355; hg19: chr1-109857815;