chr14-50047635-G-A

Variant names:

• chr14-50047635-G-A
• rs8013833
• ENST00000556019.2:n.187-46C>T

Variant summary

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

The ENST00000556019.2(LINC01588):​n.187-46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0312 in 152,600 control chromosomes in the GnomAD database, including 142 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 0.031 (142 hom., cov: 30)
  • Exomes 𝑓: 0.0029 (0 hom.)
• Consequence: LINC01588 ENST00000556019.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.374
• Publications: 0 publications found

Genes affected

LINC01588 (HGNC:27503): (long intergenic non-protein coding RNA 1588)

LINC01599 (HGNC:27285): (long intergenic non-protein coding RNA 1599)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINC01599	NR_131171.1	n.254-46C>T		intron_variant	Intron 3 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINC01588	ENST00000556019.2	n.187-46C>T		intron_variant	Intron 2 of 4	3
LINC01588	ENST00000557142.6	n.2566+5139C>T		intron_variant	Intron 2 of 6	3
LINC01588	ENST00000603228.3	n.313-46C>T		intron_variant	Intron 3 of 8	5

Frequencies

GnomAD3 genomes AF: 0.0313 AC: 4757 AN: 152138 Hom.: 142 Cov.: 30

Gnomad AFR AF: 0.0819

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0188

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00621

Gnomad FIN AF: 0.00603

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0119

Gnomad OTH AF: 0.0336

GnomAD4 exome AF: 0.00291 AC: 1 AN: 344 Hom.: 0 Cov.: 0 AF XY: 0.00420 AC XY: 1 AN XY: 238

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

African (AFR) AF: 0.00 AC: 0 AN: 14

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 12

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00385 AC: 1 AN: 260

Other (OTH) AF: 0.00 AC: 0 AN: 12

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0313 AC: 4763 AN: 152256 Hom.: 142 Cov.: 30 AF XY: 0.0301 AC XY: 2238 AN XY: 74452

African (AFR) AF: 0.0819 AC: 3403 AN: 41532

American (AMR) AF: 0.0187 AC: 286 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 75 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00601 AC: 29 AN: 4826

European-Finnish (FIN) AF: 0.00603 AC: 64 AN: 10606

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0119 AC: 807 AN: 68032

Other (OTH) AF: 0.0332 AC: 70 AN: 2108

Alfa AF: 0.0136 Hom.: 35

Bravo AF: 0.0344

Asia WGS AF: 0.00982 AC: 35 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
DANN	Benign	0.67
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs8013833; hg19: chr14-50514353;