1-109313684-G-A

Variant names:

• chr1-109313684-G-A
• rs464218
• NM_002959.7:c.*359C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 28 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORT1	NM_002959.7	MANE Select	c.*359C>T		3_prime_UTR	Exon 20 of 20	NP_002950.3
	SORT1	NM_001205228.2		c.*359C>T		3_prime_UTR	Exon 20 of 20	NP_001192157.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORT1	ENST00000256637.8	TSL:1 MANE Select	c.*359C>T		3_prime_UTR	Exon 20 of 20	ENSP00000256637.6
	SORT1	ENST00000538502.5	TSL:2	c.*359C>T		3_prime_UTR	Exon 20 of 20	ENSP00000438597.1
	SORT1	ENST00000485149.1	TSL:3	n.*117C>T		downstream_gene	N/A

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

African (AFR) AF: 0.161 AC: 469 AN: 2914

American (AMR) AF: 0.554 AC: 2624 AN: 4736

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2244 AN: 3566

East Asian (EAS) AF: 0.632 AC: 3867 AN: 6120

South Asian (SAS) AF: 0.473 AC: 7503 AN: 15868

European-Finnish (FIN) AF: 0.527 AC: 3225 AN: 6124

Middle Eastern (MID) AF: 0.568 AC: 301 AN: 530

European-Non Finnish (NFE) AF: 0.538 AC: 41545 AN: 77282

Other (OTH) AF: 0.521 AC: 3589 AN: 6886

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

African (AFR) AF: 0.170 AC: 7066 AN: 41516

American (AMR) AF: 0.527 AC: 8060 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2152 AN: 3472

East Asian (EAS) AF: 0.612 AC: 3165 AN: 5172

South Asian (SAS) AF: 0.477 AC: 2301 AN: 4828

European-Finnish (FIN) AF: 0.526 AC: 5566 AN: 10586

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36445 AN: 67970

Other (OTH) AF: 0.470 AC: 995 AN: 2116

Alfa AF: 0.507 Hom.: 58714

Bravo AF: 0.427

Asia WGS AF: 0.535 AC: 1859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.57
PhyloP100		-0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs464218; hg19: chr1-109856306;