11-121568956-T-C

Position:

• chr11-121568956-T-C

Variant summary

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

The NM_003105.6(SORL1):​c.3224-1201T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.948 in 152,272 control chromosomes in the GnomAD database, including 68,617 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 0.95 (68617 hom., cov: 32)
• Consequence: SORL1 NM_003105.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.71

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORL1	NM_003105.6	c.3224-1201T>C		intron_variant		ENST00000260197.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORL1	ENST00000260197.12	c.3224-1201T>C		intron_variant		1	NM_003105.6	P1
SORL1	ENST00000525532.5	c.56-1201T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.948 AC: 144208 AN: 152154 Hom.: 68587 Cov.: 32

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.971

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.979

Gnomad FIN AF: 0.992

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.981

Gnomad OTH AF: 0.962

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

GnomAD4 genome AF: 0.948 AC: 144295 AN: 152272 Hom.: 68617 Cov.: 32 AF XY: 0.950 AC XY: 70734 AN XY: 74438

Gnomad4 AFR AF: 0.866

Gnomad4 AMR AF: 0.971

Gnomad4 ASJ AF: 0.988

Gnomad4 EAS AF: 0.929

Gnomad4 SAS AF: 0.979

Gnomad4 FIN AF: 0.992

Gnomad4 NFE AF: 0.981

Gnomad4 OTH AF: 0.963

Alfa AF: 0.967 Hom.: 3366

Bravo AF: 0.942

Asia WGS AF: 0.951 AC: 3307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.18

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: rs1784919; hg19: chr11-121439665;