19-17510699-A-G

Position:

• chr19-17510699-A-G

Variant summary

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

The NR_147835.1(PGLS-DT):​n.547+644T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 152,036 control chromosomes in the GnomAD database, including 29,331 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 0.61 (29325 hom., cov: 32)
  • Exomes 𝑓: 0.67 (6 hom.)
• Consequence: PGLS-DT NR_147835.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

Genes affected

PGLS-DT (HGNC:55274): (PGLS divergent transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGLS-DT	NR_147835.1	n.547+644T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGLS-DT	ENST00000596643.5	n.547+644T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92697 AN: 151894 Hom.: 29264 Cov.: 32

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.625

GnomAD4 exome AF: 0.667 AC: 16 AN: 24 Hom.: 6 Cov.: 0 AF XY: 0.611 AC XY: 11 AN XY: 18

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.875

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.611 AC: 92814 AN: 152012 Hom.: 29325 Cov.: 32 AF XY: 0.615 AC XY: 45668 AN XY: 74314

Gnomad4 AFR AF: 0.783

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.626

Alfa AF: 0.539 Hom.: 44347

Bravo AF: 0.624

Asia WGS AF: 0.512 AC: 1784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1078000; hg19: chr19-17621508;