11-121451045-T-C

Variant names:

• chr11-121451045-T-C
• rs4935774
• ENST00000529160.2:n.294-1146A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000501964.1(SORL1-AS1):​n.340-1146A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 151,946 control chromosomes in the GnomAD database, including 9,056 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 0.31 (9056 hom., cov: 31)
• Consequence: SORL1-AS1 ENST00000501964.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 17 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000501964.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORL1-AS1	NR_183636.1	MANE Select	n.294-1146A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORL1-AS1	ENST00000529160.2	TSL:2 MANE Select	n.294-1146A>G		intron	N/A
	SORL1-AS1	ENST00000501964.1	TSL:2	n.340-1146A>G		intron	N/A
	SORL1-AS1	ENST00000715254.2		n.885+234A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47391 AN: 151828 Hom.: 9021 Cov.: 31

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.312 AC: 47481 AN: 151946 Hom.: 9056 Cov.: 31 AF XY: 0.304 AC XY: 22609 AN XY: 74268

African (AFR) AF: 0.545 AC: 22549 AN: 41388

American (AMR) AF: 0.267 AC: 4071 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 726 AN: 3472

East Asian (EAS) AF: 0.181 AC: 936 AN: 5166

South Asian (SAS) AF: 0.150 AC: 722 AN: 4824

European-Finnish (FIN) AF: 0.181 AC: 1908 AN: 10560

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15699 AN: 67960

Other (OTH) AF: 0.304 AC: 640 AN: 2102

Alfa AF: 0.249 Hom.: 9356

Bravo AF: 0.339

Asia WGS AF: 0.192 AC: 668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.57
PhyloP100		-1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4935774; hg19: chr11-121321754;