1-109344569-T-C

Variant summary

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

The NM_002959.7(SORT1):c.963+1182A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,130 control chromosomes in the GnomAD database, including 13,217 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 0.38 (13217 hom., cov: 32)
• Consequence: SORT1 NM_002959.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORT1	NM_002959.7	c.963+1182A>G		intron_variant		ENST00000256637.8
SORT1	NM_001205228.2	c.552+1182A>G		intron_variant
SORT1	XM_005271100.3	c.960+1182A>G		intron_variant
SORT1	XM_005271101.4	c.555+1182A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORT1	ENST00000256637.8	c.963+1182A>G		intron_variant		1	NM_002959.7	P1
SORT1	ENST00000538502.5	c.552+1182A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57173 AN: 152010 Hom.: 13208 Cov.: 32

Gnomad AFR AF: 0.0958

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.376 AC: 57194 AN: 152130 Hom.: 13217 Cov.: 32 AF XY: 0.380 AC XY: 28272 AN XY: 74356

Gnomad4 AFR AF: 0.0956

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.417

Alfa AF: 0.440 Hom.: 9546

Bravo AF: 0.367

Asia WGS AF: 0.496 AC: 1724 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.3
Dann	Benign	0.42

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: rs4970843; hg19: chr1-109887191;