rs4935774

Positions:

• chr11-121451045-T-C
• chr11-121451045-T-G

Variant summary

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

The NR_183636.1(SORL1-AS1):​n.294-1146A>G variant causes a intron, non coding transcript 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 NR_183636.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORL1-AS1	NR_183636.1	n.294-1146A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORL1-AS1	ENST00000501964.1	n.340-1146A>G		intron_variant, non_coding_transcript_variant		2
SORL1-AS1	ENST00000529160.1	n.246-1146A>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.304

Alfa AF: 0.243 Hom.: 6733

Bravo AF: 0.339

Asia WGS AF: 0.192 AC: 668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4935774; hg19: chr11-121321754;