rs2142824

Positions:

• chr22-36537621-G-A

Variant summary

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

The 22-36537621-G-A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 732,054 control chromosomes in the GnomAD database, including 52,632 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 0.39 (11927 hom., cov: 31)
  • Exomes 𝑓: 0.37 (40705 hom.)
• Consequence: ENST00000339367.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980

Genes affected

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000339367.4			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59659 AN: 151948 Hom.: 11902 Cov.: 31

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.368

GnomAD4 exome AF: 0.372 AC: 215568 AN: 579988 Hom.: 40705 Cov.: 3 AF XY: 0.372 AC XY: 117626 AN XY: 315824

Gnomad4 AFR exome AF: 0.451

Gnomad4 AMR exome AF: 0.365

Gnomad4 ASJ exome AF: 0.402

Gnomad4 EAS exome AF: 0.226

Gnomad4 SAS exome AF: 0.391

Gnomad4 FIN exome AF: 0.373

Gnomad4 NFE exome AF: 0.376

Gnomad4 OTH exome AF: 0.376

GnomAD4 genome AF: 0.393 AC: 59723 AN: 152066 Hom.: 11927 Cov.: 31 AF XY: 0.390 AC XY: 28999 AN XY: 74326

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.364

Alfa AF: 0.387 Hom.: 2309

Bravo AF: 0.394

Asia WGS AF: 0.300 AC: 1041 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.18
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2142824; hg19: chr22-36933668; COSMIC: COSV59546486;