chr1-161363768-A-G

Position:

• chr1-161363768-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The variant allele was found at a frequency of 0.112 in 232,898 control chromosomes in the GnomAD database, including 2,186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1420 hom., cov: 32)
  • Exomes 𝑓: 0.10 (766 hom.)
• Consequence: intergenic_region
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0340

Genes affected

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 1-161363768-A-G is Benign according to our data. Variant chr1-161363768-A-G is described in ClinVar as [Benign]. Clinvar id is 293347.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.161363768A>G		intergenic_region

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17801 AN: 152064 Hom.: 1417 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0687

Gnomad ASJ AF: 0.0282

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0643

Gnomad OTH AF: 0.0930

GnomAD4 exome AF: 0.101 AC: 8183 AN: 80718 Hom.: 766 Cov.: 0 AF XY: 0.0976 AC XY: 3622 AN XY: 37124

Gnomad4 AFR exome AF: 0.223

Gnomad4 AMR exome AF: 0.0635

Gnomad4 ASJ exome AF: 0.0310

Gnomad4 EAS exome AF: 0.303

Gnomad4 SAS exome AF: 0.209

Gnomad4 FIN exome AF: 0.0517

Gnomad4 NFE exome AF: 0.0568

Gnomad4 OTH exome AF: 0.0767

GnomAD4 genome AF: 0.117 AC: 17823 AN: 152180 Hom.: 1420 Cov.: 32 AF XY: 0.120 AC XY: 8914 AN XY: 74418

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.0685

Gnomad4 ASJ AF: 0.0282

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.0643

Gnomad4 OTH AF: 0.0920

Alfa AF: 0.0641 Hom.: 405

Bravo AF: 0.115

Asia WGS AF: 0.202 AC: 698 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary pheochromocytoma-paraganglioma Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.28
DANN	Benign	0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3935401; hg19: chr1-161333558;