rs133376

chr22-42070901-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The 22-42070901-C-T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 166,156 control chromosomes in the GnomAD database, including 13,464 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (11709 hom., cov: 34)
  • Exomes 𝑓: 0.49 (1755 hom.)
• Consequence: ENST00000662963.1 upstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.190

Genes affected

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 22-42070901-C-T is Benign according to our data. Variant chr22-42070901-C-T is described in ClinVar as [Benign]. Clinvar id is 684292.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.48 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
	ENST00000662963.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54592 AN: 152072 Hom.: 11697 Cov.: 34

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.383

GnomAD4 exome AF: 0.491 AC: 6860 AN: 13966 Hom.: 1755 AF XY: 0.492 AC XY: 3740 AN XY: 7602

Gnomad4 AFR exome AF: 0.169

Gnomad4 AMR exome AF: 0.541

Gnomad4 ASJ exome AF: 0.380

Gnomad4 EAS exome AF: 0.381

Gnomad4 SAS exome AF: 0.498

Gnomad4 FIN exome AF: 0.590

Gnomad4 NFE exome AF: 0.492

Gnomad4 OTH exome AF: 0.486

GnomAD4 genome AF: 0.359 AC: 54610 AN: 152190 Hom.: 11709 Cov.: 34 AF XY: 0.365 AC XY: 27183 AN XY: 74398

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.389

Alfa AF: 0.381 Hom.: 1980

Bravo AF: 0.350

Asia WGS AF: 0.414 AC: 1438 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	15
Dann	Benign	0.92

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs133376; hg19: chr22-42466905;