16-90043303-A-G

Position:

• chr16-90043303-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001481.3(GAS8):​c.1395A>G​(p.Thr465=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 1,612,574 control chromosomes in the GnomAD database, including 496,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T465T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.82 (52147 hom., cov: 33)
  • Exomes 𝑓: 0.78 (444443 hom.)
• Consequence: GAS8 NM_001481.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.69

Genes affected

GAS8 (HGNC:4166): (growth arrest specific 8) This gene includes 11 exons spanning 25 kb and maps to a region of chromosome 16 that is sometimes deleted in breast and prostrate cancer. The second intron contains an apparently intronless gene, C16orf3, that is transcribed in the opposite orientation. This gene is a putative tumor suppressor gene. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

URAHP (HGNC:43695): (urate (hydroxyiso-) hydrolase, pseudogene) Predicted to enable hydroxyisourate hydrolase activity. Predicted to be involved in allantoin metabolic process; purine-containing compound catabolic process; and urate catabolic process. Predicted to be active in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 16-90043303-A-G is Benign according to our data. Variant chr16-90043303-A-G is described in ClinVar as [Benign]. Clinvar id is 402894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.69 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAS8	NM_001481.3	c.1395A>G	p.Thr465=	synonymous_variant	11/11	ENST00000268699.9
URAHP	NR_027335.2	n.692+345T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAS8	ENST00000268699.9	c.1395A>G	p.Thr465=	synonymous_variant	11/11	1	NM_001481.3	P4
URAHP	ENST00000409873.5	n.692+345T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.822 AC: 125028 AN: 152026 Hom.: 52085 Cov.: 33

Gnomad AFR AF: 0.956

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.823

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.821

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.774

GnomAD3 exomes AF: 0.795 AC: 196742 AN: 247578 Hom.: 78838 AF XY: 0.786 AC XY: 105490 AN XY: 134240

Gnomad AFR exome AF: 0.963

Gnomad AMR exome AF: 0.841

Gnomad ASJ exome AF: 0.832

Gnomad EAS exome AF: 0.818

Gnomad SAS exome AF: 0.769

Gnomad FIN exome AF: 0.824

Gnomad NFE exome AF: 0.752

Gnomad OTH exome AF: 0.767

GnomAD4 exome AF: 0.779 AC: 1137357 AN: 1460430 Hom.: 444443 Cov.: 57 AF XY: 0.777 AC XY: 564604 AN XY: 726514

Gnomad4 AFR exome AF: 0.961

Gnomad4 AMR exome AF: 0.837

Gnomad4 ASJ exome AF: 0.837

Gnomad4 EAS exome AF: 0.828

Gnomad4 SAS exome AF: 0.774

Gnomad4 FIN exome AF: 0.820

Gnomad4 NFE exome AF: 0.766

Gnomad4 OTH exome AF: 0.783

GnomAD4 genome AF: 0.823 AC: 125147 AN: 152144 Hom.: 52147 Cov.: 33 AF XY: 0.823 AC XY: 61195 AN XY: 74358

Gnomad4 AFR AF: 0.956

Gnomad4 AMR AF: 0.786

Gnomad4 ASJ AF: 0.840

Gnomad4 EAS AF: 0.823

Gnomad4 SAS AF: 0.784

Gnomad4 FIN AF: 0.821

Gnomad4 NFE AF: 0.755

Gnomad4 OTH AF: 0.769

Alfa AF: 0.770 Hom.: 16858

Bravo AF: 0.829

Asia WGS AF: 0.804 AC: 2800 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia 33 Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.031
DANN	Benign	0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs3743825; hg19: chr16-90109711;