1-109344569-T-C

Variant names:

• chr1-109344569-T-C
• rs4970843
• NM_002959.7:c.963+1182A>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.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
• Publications: 19 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 (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORT1	NM_002959.7	c.963+1182A>G		intron_variant	Intron 8 of 19	ENST00000256637.8	NP_002950.3
SORT1	NM_001205228.2	c.552+1182A>G		intron_variant	Intron 8 of 19		NP_001192157.1
SORT1	XM_005271100.3	c.960+1182A>G		intron_variant	Intron 8 of 19		XP_005271157.1
SORT1	XM_005271101.4	c.555+1182A>G		intron_variant	Intron 8 of 19		XP_005271158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORT1	ENST00000256637.8	c.963+1182A>G		intron_variant	Intron 8 of 19	1	NM_002959.7	ENSP00000256637.6
SORT1	ENST00000538502.5	c.552+1182A>G		intron_variant	Intron 8 of 19	2		ENSP00000438597.1

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

African (AFR) AF: 0.0956 AC: 3970 AN: 41546

American (AMR) AF: 0.486 AC: 7419 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2001 AN: 3470

East Asian (EAS) AF: 0.601 AC: 3102 AN: 5160

South Asian (SAS) AF: 0.439 AC: 2118 AN: 4828

European-Finnish (FIN) AF: 0.488 AC: 5149 AN: 10554

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32129 AN: 67996

Other (OTH) AF: 0.417 AC: 880 AN: 2112

Alfa AF: 0.442 Hom.: 10390

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
PhyloP100		-0.49
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: rs4970843; hg19: chr1-109887191;