rs12526133

Variant names:

• chr6-14281792-C-T
• rs12526133
• ENST00000427276.1:n.1487G>A

Variant summary

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

The ENST00000427276.1(LINC01108):​n.1487G>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 0.423 in 152,042 control chromosomes in the GnomAD database, including 16,444 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 0.42 (16444 hom., cov: 32)
  • Exomes 𝑓: 0.33 (0 hom.)
• Consequence: LINC01108 ENST00000427276.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.428
• Publications: 5 publications found

Genes affected

LINC01108 (HGNC:49234): (long intergenic non-protein coding RNA 1108)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000427276.1. 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
	LINC01108	NR_108096.1		n.2032G>A		non_coding_transcript_exon	Exon 3 of 3
	LINC01108	NR_108097.1		n.1796G>A		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC01108	ENST00000427276.1	TSL:2	n.1487G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64291 AN: 151918 Hom.: 16438 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.472

GnomAD4 exome AF: 0.333 AC: 2 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

⚠️ 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: 0.333 AC: 2 AN: 6

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.423 AC: 64329 AN: 152036 Hom.: 16444 Cov.: 32 AF XY: 0.423 AC XY: 31470 AN XY: 74312

African (AFR) AF: 0.142 AC: 5906 AN: 41468

American (AMR) AF: 0.537 AC: 8202 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1919 AN: 3466

East Asian (EAS) AF: 0.174 AC: 899 AN: 5160

South Asian (SAS) AF: 0.388 AC: 1866 AN: 4812

European-Finnish (FIN) AF: 0.549 AC: 5802 AN: 10560

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.562 AC: 38190 AN: 67972

Other (OTH) AF: 0.470 AC: 993 AN: 2112

Alfa AF: 0.492 Hom.: 7192

Bravo AF: 0.410

Asia WGS AF: 0.267 AC: 933 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	3.4
DANN	Benign	0.73
PhyloP100		-0.43

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs12526133;

hg19: chr6-14282023;