chr1-109315193-A-C

Position:

• chr1-109315193-A-C

Variant summary

Our verdict is Benign. Variant got -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

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]

SORT1 (HGNC:):

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORT1	NM_002959.7	c.2251-415T>G		intron_variant		ENST00000256637.8	NP_002950.3
SORT1	NM_001205228.2	c.1840-415T>G		intron_variant			NP_001192157.1
SORT1	XM_005271100.3	c.2248-415T>G		intron_variant			XP_005271157.1
SORT1	XM_005271101.4	c.1843-415T>G		intron_variant			XP_005271158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORT1	ENST00000256637.8	c.2251-415T>G		intron_variant		1	NM_002959.7	ENSP00000256637.6
SORT1	ENST00000538502.5	c.1840-415T>G		intron_variant		2		ENSP00000438597.1
SORT1	ENST00000485149.1	n.79-415T>G		intron_variant		3

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

Gnomad4 AFR AF: 0.0110

Gnomad4 AMR AF: 0.0226

Gnomad4 ASJ AF: 0.0164

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.0174

Gnomad4 FIN AF: 0.0754

Gnomad4 NFE AF: 0.0583

Gnomad4 OTH AF: 0.0307

Alfa AF: 0.0479 Hom.: 58

Bravo AF: 0.0341

Asia WGS AF: 0.00837 AC: 29 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	6.1
DANN	Benign	0.72

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: rs17585355; hg19: chr1-109857815;