8-40299341-A-T

Position:

• chr8-40299341-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000669842.1(SIRLNT):​n.185T>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 0.0328 in 152,220 control chromosomes in the GnomAD database, including 133 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 0.033 (133 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SIRLNT ENST00000669842.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78

Genes affected

SIRLNT (HGNC:53902): (SIRT1 regulating lncRNA tumor promoter)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIRLNT	ENST00000669842.1	n.185T>A		non_coding_transcript_exon_variant	2/2
SIRLNT	ENST00000521363.1	n.281T>A		non_coding_transcript_exon_variant	3/3	2
SIRLNT	ENST00000522486.1	n.239T>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0328 AC: 4989 AN: 152102 Hom.: 133 Cov.: 33

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.0187

Gnomad AMR AF: 0.0352

Gnomad ASJ AF: 0.0473

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0905

Gnomad FIN AF: 0.0235

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0351

Gnomad OTH AF: 0.0392

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0328 AC: 4991 AN: 152220 Hom.: 133 Cov.: 33 AF XY: 0.0335 AC XY: 2493 AN XY: 74450

Gnomad4 AFR AF: 0.0132

Gnomad4 AMR AF: 0.0351

Gnomad4 ASJ AF: 0.0473

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.0901

Gnomad4 FIN AF: 0.0235

Gnomad4 NFE AF: 0.0351

Gnomad4 OTH AF: 0.0384

Alfa AF: 0.0126 Hom.: 9

Bravo AF: 0.0314

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.7
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2272773; hg19: chr8-40156860;