rs464218

Positions:

• chr1-109313684-G-A

Variant summary

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

The NM_002959.7(SORT1):​c.*359C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 276,184 control chromosomes in the GnomAD database, including 34,608 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 0.44 (16567 hom., cov: 33)
  • Exomes 𝑓: 0.53 (18041 hom.)
• Consequence: SORT1 NM_002959.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.690

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORT1	NM_002959.7	c.*359C>T		3_prime_UTR_variant	20/20	ENST00000256637.8	NP_002950.3
SORT1	NM_001205228.2	c.*359C>T		3_prime_UTR_variant	20/20		NP_001192157.1
SORT1	XM_005271100.3	c.*359C>T		3_prime_UTR_variant	20/20		XP_005271157.1
SORT1	XM_005271101.4	c.*359C>T		3_prime_UTR_variant	20/20		XP_005271158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORT1	ENST00000256637.8	c.*359C>T		3_prime_UTR_variant	20/20	1	NM_002959.7	ENSP00000256637	P1
SORT1	ENST00000538502.5	c.*359C>T		3_prime_UTR_variant	20/20	2		ENSP00000438597

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66245 AN: 152040 Hom.: 16558 Cov.: 33

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.466

GnomAD4 exome AF: 0.527 AC: 65367 AN: 124026 Hom.: 18041 Cov.: 0 AF XY: 0.524 AC XY: 34443 AN XY: 65682

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.554

Gnomad4 ASJ exome AF: 0.629

Gnomad4 EAS exome AF: 0.632

Gnomad4 SAS exome AF: 0.473

Gnomad4 FIN exome AF: 0.527

Gnomad4 NFE exome AF: 0.538

Gnomad4 OTH exome AF: 0.521

GnomAD4 genome AF: 0.436 AC: 66267 AN: 152158 Hom.: 16567 Cov.: 33 AF XY: 0.437 AC XY: 32536 AN XY: 74392

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.612

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.470

Alfa AF: 0.533 Hom.: 35519

Bravo AF: 0.427

Asia WGS AF: 0.535 AC: 1859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs464218; hg19: chr1-109856306;