rs8017950

Variant names:

• chr14-100657531-G-A
• rs8017950
• ENST00000360899.3:n.287G>A

Variant summary

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

The ENST00000360899.3(LINC00523):​n.287G>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 0.768 in 152,224 control chromosomes in the GnomAD database, including 48,212 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 0.77 (48210 hom., cov: 34)
  • Exomes 𝑓: 0.60 (2 hom.)
• Consequence: LINC00523 ENST00000360899.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151

Genes affected

LINC00523 (HGNC:20117): (long intergenic non-protein coding RNA 523)

ACMG classification

Our verdict: Benign. The variant received -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 = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINC00523	NR_024096.1	n.264G>A		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINC00523	ENST00000360899.3	n.287G>A		non_coding_transcript_exon_variant	Exon 1 of 2	1
LINC00523	ENST00000553623.1	n.174G>A		non_coding_transcript_exon_variant	Exon 1 of 2	3
LINC00523	ENST00000556697.1	n.282G>A		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116907 AN: 152096 Hom.: 48208 Cov.: 34

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.969

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.963

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.867

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.808

GnomAD4 exome AF: 0.600 AC: 6 AN: 10 Hom.: 2 Cov.: 0 AF XY: 0.625 AC XY: 5 AN XY: 8

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.667 AC: 4 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 1.00 AC: 2 AN: 2

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.768 AC: 116941 AN: 152214 Hom.: 48210 Cov.: 34 AF XY: 0.761 AC XY: 56596 AN XY: 74412

African (AFR) AF: 0.526 AC: 21831 AN: 41502

American (AMR) AF: 0.652 AC: 9973 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.963 AC: 3340 AN: 3470

East Asian (EAS) AF: 0.324 AC: 1675 AN: 5164

South Asian (SAS) AF: 0.750 AC: 3614 AN: 4818

European-Finnish (FIN) AF: 0.867 AC: 9201 AN: 10614

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.947 AC: 64460 AN: 68036

Other (OTH) AF: 0.800 AC: 1692 AN: 2114

Alfa AF: 0.893 Hom.: 99152

Bravo AF: 0.738

Asia WGS AF: 0.517 AC: 1802 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	2.8
DANN	Benign	0.79
PhyloP100		-0.15

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8017950; hg19: chr14-101123868;