11-121564878-T-C

Variant names:

• chr11-121564878-T-C
• rs11218343
• NM_003105.6:c.3050-2062T>C

Variant summary

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

The NM_003105.6(SORL1):​c.3050-2062T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0629 in 152,222 control chromosomes in the GnomAD database, including 467 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 0.063 (467 hom., cov: 32)
• Consequence: SORL1 NM_003105.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORL1	NM_003105.6	c.3050-2062T>C		intron_variant	Intron 21 of 47	ENST00000260197.12	NP_003096.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORL1	ENST00000260197.12	c.3050-2062T>C		intron_variant	Intron 21 of 47	1	NM_003105.6	ENSP00000260197.6

Frequencies

GnomAD3 genomes AF: 0.0629 AC: 9561 AN: 152106 Hom.: 468 Cov.: 32

Gnomad AFR AF: 0.0801

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0688

Gnomad ASJ AF: 0.0640

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.0734

Gnomad FIN AF: 0.0249

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0390

Gnomad OTH AF: 0.0559

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

GnomAD4 genome AF: 0.0629 AC: 9570 AN: 152222 Hom.: 467 Cov.: 32 AF XY: 0.0637 AC XY: 4744 AN XY: 74434

Gnomad4 AFR AF: 0.0803

Gnomad4 AMR AF: 0.0688

Gnomad4 ASJ AF: 0.0640

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.0725

Gnomad4 FIN AF: 0.0249

Gnomad4 NFE AF: 0.0390

Gnomad4 OTH AF: 0.0553

Alfa AF: 0.0273 Hom.: 21

Bravo AF: 0.0687

Asia WGS AF: 0.165 AC: 573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.8
DANN	Benign	0.44

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: rs11218343; hg19: chr11-121435587;