rs34223104

chr19-40991224-T-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP5 BP4 BS1_Supporting BS2

The variant allele was found at a frequency of 0.011 in 1,487,700 control chromosomes in the GnomAD database, including 174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Pathogenic (no stars).

• Frequency:
  • Genomes: 𝑓 0.016 (44 hom., cov: 31)
  • Exomes 𝑓: 0.010 (130 hom.)
• Consequence: Unknown
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PP5: Variant 19-40991224-T-C is Pathogenic according to our data. Variant chr19-40991224-T-C is described in Lovd as [Pathogenic].
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).. Strength limited to SUPPORTING due to the PP5.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0162 (2469/152140) while in subpopulation AFR AF= 0.0295 (1221/41456). AF 95% confidence interval is 0.0281. There are 44 homozygotes in gnomad4. There are 1216 alleles in male gnomad4 subpopulation. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd at 45 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.0162 AC: 2461 AN: 152022 Hom.: 45 Cov.: 31

Gnomad AFR AF: 0.0294

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0189

Gnomad FIN AF: 0.00707

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.0172

GnomAD4 exome AF: 0.0104 AC: 13856 AN: 1335560 Hom.: 130 Cov.: 20 AF XY: 0.0107 AC XY: 7188 AN XY: 670682

Gnomad4 AFR exome AF: 0.0302

Gnomad4 AMR exome AF: 0.00948

Gnomad4 ASJ exome AF: 0.0212

Gnomad4 EAS exome AF: 0.00139

Gnomad4 SAS exome AF: 0.0170

Gnomad4 FIN exome AF: 0.00755

Gnomad4 NFE exome AF: 0.00928

Gnomad4 OTH exome AF: 0.0125

GnomAD4 genome AF: 0.0162 AC: 2469 AN: 152140 Hom.: 44 Cov.: 31 AF XY: 0.0164 AC XY: 1216 AN XY: 74368

Gnomad4 AFR AF: 0.0295

Gnomad4 AMR AF: 0.0132

Gnomad4 ASJ AF: 0.0190

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.0193

Gnomad4 FIN AF: 0.00707

Gnomad4 NFE AF: 0.0111

Gnomad4 OTH AF: 0.0171

Alfa AF: 0.0135 Hom.: 3

Bravo AF: 0.0172

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	12
Dann	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34223104; hg19: chr19-41497129;