chr11-121471378-G-A

Position:

• chr11-121471378-G-A

Variant summary

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

The NM_003105.6(SORL1):​c.402+1255G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,040 control chromosomes in the GnomAD database, including 8,809 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 0.32 (8809 hom., cov: 32)
• Consequence: SORL1 NM_003105.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORL1	NM_003105.6	c.402+1255G>A		intron_variant		ENST00000260197.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORL1	ENST00000260197.12	c.402+1255G>A		intron_variant		1	NM_003105.6	P1
SORL1	ENST00000532451.1	n.354+1255G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48292 AN: 151922 Hom.: 8812 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.317 AC: 48271 AN: 152040 Hom.: 8809 Cov.: 32 AF XY: 0.317 AC XY: 23540 AN XY: 74290

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.321

Alfa AF: 0.387 Hom.: 15533

Bravo AF: 0.298

Asia WGS AF: 0.205 AC: 713 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	0.057
DANN	Benign	0.73

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: rs11218301; hg19: chr11-121342087;