15-95210724-C-T

Variant names:

• chr15-95210724-C-T
• rs290369
• ENST00000556899.2:n.1165-83G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000614853.2(LETR1):​n.620-83G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 151,878 control chromosomes in the GnomAD database, including 20,502 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 0.48 (20502 hom., cov: 31)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: LETR1 ENST00000614853.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91
• Publications: 1 publications found

Genes affected

LETR1 (HGNC:49597): (lymphatic endothelial transcriptional regulator lncRNA 1)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000614853.2. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LETR1	ENST00000556899.2	TSL:4	n.1165-83G>A		intron	N/A
	LETR1	ENST00000614853.2	TSL:3	n.620-83G>A		intron	N/A
	LETR1	ENST00000658041.2		n.506-83G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73263 AN: 151758 Hom.: 20463 Cov.: 31

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.445

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

⚠️ 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: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

⚠️ 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: 0.483 AC: 73354 AN: 151876 Hom.: 20502 Cov.: 31 AF XY: 0.477 AC XY: 35396 AN XY: 74196

African (AFR) AF: 0.792 AC: 32804 AN: 41444

American (AMR) AF: 0.352 AC: 5359 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1284 AN: 3472

East Asian (EAS) AF: 0.323 AC: 1660 AN: 5140

South Asian (SAS) AF: 0.412 AC: 1982 AN: 4816

European-Finnish (FIN) AF: 0.382 AC: 4029 AN: 10540

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24886 AN: 67908

Other (OTH) AF: 0.442 AC: 933 AN: 2112

Alfa AF: 0.421 Hom.: 2134

Bravo AF: 0.494

Asia WGS AF: 0.363 AC: 1262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	18
DANN	Benign	0.65
PhyloP100		1.9

Splicing

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

Other links and lift over

dbSNP: rs290369; hg19: chr15-95753953;