11-121452768-G-T

Variant names:

• chr11-121452768-G-T
• rs578506
• ENST00000529160.2:n.200C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000529160.2(SORL1-AS1):​n.200C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000135 in 445,730 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: SORL1-AS1 ENST00000529160.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376
• Publications: 9 publications found

Genes affected

SORL1-AS1 (HGNC:55594): (SORL1 antisense RNA 1)

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 Gene-Disease associations (from GenCC):

• early-onset autosomal dominant Alzheimer disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000529160.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORL1-AS1	NR_183636.1	MANE Select	n.200C>A		non_coding_transcript_exon	Exon 1 of 3
	SORL1	NM_003105.6	MANE Select	c.285+152G>T		intron	N/A	NP_003096.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORL1-AS1	ENST00000529160.2	TSL:2 MANE Select	n.200C>A		non_coding_transcript_exon	Exon 1 of 3
	SORL1	ENST00000260197.12	TSL:1 MANE Select	c.285+152G>T		intron	N/A	ENSP00000260197.6
	SORL1	ENST00000532451.1	TSL:1	n.237+152G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000135 AC: 6 AN: 445730 Hom.: 0 Cov.: 6 AF XY: 0.0000218 AC XY: 5 AN XY: 229800

African (AFR) AF: 0.00 AC: 0 AN: 9550

American (AMR) AF: 0.00 AC: 0 AN: 8378

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12064

East Asian (EAS) AF: 0.000255 AC: 6 AN: 23546

South Asian (SAS) AF: 0.00 AC: 0 AN: 32152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28478

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2002

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 304854

Other (OTH) AF: 0.00 AC: 0 AN: 24706

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.87
PhyloP100		0.38
PromoterAI		-0.041	Neutral

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: rs578506; hg19: chr11-121323477;