11-121500007-C-T

Position:

• chr11-121500007-C-T

Variant summary

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

The NM_003105.6(SORL1):​c.939+2958C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,216 control chromosomes in the GnomAD database, including 1,500 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 0.12 (1500 hom., cov: 33)
• Consequence: SORL1 NM_003105.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570

Genes affected

SORL1 (HGNC:11185): (sortilin related receptor 1) This gene encodes a mosaic protein that belongs to at least two families: the vacuolar protein sorting 10 (VPS10) domain-containing receptor family, and the low density lipoprotein receptor (LDLR) family. The encoded protein also contains fibronectin type III repeats and an epidermal growth factor repeat. The encoded preproprotein is proteolytically processed to generate the mature receptor, which likely plays roles in endocytosis and sorting. Mutations in this gene may be associated with Alzheimer's disease. [provided by RefSeq, Feb 2016]

SORL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORL1	NM_003105.6	c.939+2958C>T		intron_variant		ENST00000260197.12	NP_003096.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORL1	ENST00000260197.12	c.939+2958C>T		intron_variant		1	NM_003105.6	ENSP00000260197.6
SORL1	ENST00000532451.1	n.891+2958C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19009 AN: 152098 Hom.: 1496 Cov.: 33

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.0976

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.0920

Gnomad FIN AF: 0.0350

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.125 AC: 19024 AN: 152216 Hom.: 1500 Cov.: 33 AF XY: 0.121 AC XY: 9003 AN XY: 74426

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.0974

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0925

Gnomad4 FIN AF: 0.0350

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.131

Alfa AF: 0.115 Hom.: 225

Bravo AF: 0.135

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs753780; hg19: chr11-121370716;