rs1614735

Positions:

• chr11-121622292-T-G

Variant summary

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

The NM_003105.6(SORL1):​c.6171+24T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 1,372,548 control chromosomes in the GnomAD database, including 153,593 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 0.37 (12346 hom., cov: 32)
  • Exomes 𝑓: 0.47 (141247 hom.)
• Consequence: SORL1 NM_003105.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

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=-0.52).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORL1	NM_003105.6	c.6171+24T>G		intron_variant		ENST00000260197.12	NP_003096.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORL1	ENST00000260197.12	c.6171+24T>G		intron_variant		1	NM_003105.6	ENSP00000260197	P1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55891 AN: 151828 Hom.: 12354 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.416

GnomAD3 exomes AF: 0.405 AC: 97765 AN: 241624 Hom.: 21670 AF XY: 0.412 AC XY: 53959 AN XY: 130886

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.348

Gnomad ASJ exome AF: 0.570

Gnomad EAS exome AF: 0.126

Gnomad SAS exome AF: 0.342

Gnomad FIN exome AF: 0.451

Gnomad NFE exome AF: 0.499

Gnomad OTH exome AF: 0.457

GnomAD4 exome AF: 0.470 AC: 573500 AN: 1220602 Hom.: 141247 Cov.: 16 AF XY: 0.467 AC XY: 288812 AN XY: 618314

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.358

Gnomad4 ASJ exome AF: 0.577

Gnomad4 EAS exome AF: 0.143

Gnomad4 SAS exome AF: 0.346

Gnomad4 FIN exome AF: 0.449

Gnomad4 NFE exome AF: 0.511

Gnomad4 OTH exome AF: 0.452

GnomAD4 genome AF: 0.368 AC: 55887 AN: 151946 Hom.: 12346 Cov.: 32 AF XY: 0.365 AC XY: 27117 AN XY: 74238

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.412

Alfa AF: 0.468 Hom.: 23904

Bravo AF: 0.355

Asia WGS AF: 0.245 AC: 850 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Benign	0.90

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: rs1614735; hg19: chr11-121493001; COSMIC: COSV52753605; COSMIC: COSV52753605;