rs12606608

Variant names:

• chr18-56188320-C-T
• rs12606608
• ENST00000382897.2:n.530G>A

Variant summary

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

The ENST00000382897.2(LINC01539):​n.530G>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 0.522 in 151,980 control chromosomes in the GnomAD database, including 21,731 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 0.52 (21727 hom., cov: 31)
  • Exomes 𝑓: 0.50 (4 hom.)
• Consequence: LINC01539 ENST00000382897.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.852
• Publications: 4 publications found

Genes affected

LINC01539 (HGNC:51307): (long intergenic non-protein coding RNA 1539)

LINC03069 (HGNC:56641): (long intergenic non-protein coding RNA 3069)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINC03069	NR_148972.1	n.530G>A		non_coding_transcript_exon_variant	Exon 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINC01539	ENST00000382897.2	n.530G>A		non_coding_transcript_exon_variant	Exon 2 of 9	2
LINC01539	ENST00000715823.1	n.215G>A		non_coding_transcript_exon_variant	Exon 1 of 4
LINC01539	ENST00000765111.1	n.186G>A		non_coding_transcript_exon_variant	Exon 2 of 5

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79219 AN: 151840 Hom.: 21718 Cov.: 31

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.558

GnomAD4 exome AF: 0.500 AC: 11 AN: 22 Hom.: 4 Cov.: 0 AF XY: 0.438 AC XY: 7 AN XY: 16

⚠️ 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) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.556 AC: 10 AN: 18

Other (OTH) AF: 0.250 AC: 1 AN: 4

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000009), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.522 AC: 79256 AN: 151958 Hom.: 21727 Cov.: 31 AF XY: 0.527 AC XY: 39120 AN XY: 74256

African (AFR) AF: 0.343 AC: 14208 AN: 41424

American (AMR) AF: 0.568 AC: 8676 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2072 AN: 3466

East Asian (EAS) AF: 0.839 AC: 4322 AN: 5152

South Asian (SAS) AF: 0.551 AC: 2659 AN: 4824

European-Finnish (FIN) AF: 0.597 AC: 6296 AN: 10552

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39304 AN: 67960

Other (OTH) AF: 0.561 AC: 1183 AN: 2108

Alfa AF: 0.565 Hom.: 31005

Bravo AF: 0.512

Asia WGS AF: 0.649 AC: 2256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.69
PhyloP100		-0.85

Splicing

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

Other links and lift over

dbSNP: rs12606608; hg19: chr18-53855551;