16-90040338-C-T

Variant names:

• chr16-90040338-C-T
• rs61734731
• NM_001481.3:c.1050C>T

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.1050C>T​(p.Thr350Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0536 in 1,601,376 control chromosomes in the GnomAD database, including 2,686 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (145 hom., cov: 32)
  • Exomes 𝑓: 0.055 (2541 hom.)
• Consequence: GAS8 NM_001481.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -5.60

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:):

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=-0.93).
• BP6: Variant 16-90040338-C-T is Benign according to our data. Variant chr16-90040338-C-T is described in ClinVar as [Benign]. Clinvar id is 402893.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.6 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAS8	NM_001481.3	c.1050C>T	p.Thr350Thr	synonymous_variant	Exon 9 of 11	ENST00000268699.9	NP_001472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAS8	ENST00000268699.9	c.1050C>T	p.Thr350Thr	synonymous_variant	Exon 9 of 11	1	NM_001481.3	ENSP00000268699.4

Frequencies

GnomAD3 genomes AF: 0.0409 AC: 6220 AN: 152184 Hom.: 145 Cov.: 32

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0187

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.0386

Gnomad SAS AF: 0.0207

Gnomad FIN AF: 0.0582

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0615

Gnomad OTH AF: 0.0283

GnomAD3 exomes AF: 0.0395 AC: 9004 AN: 228100 Hom.: 242 AF XY: 0.0397 AC XY: 4896 AN XY: 123304

Gnomad AFR exome AF: 0.0113

Gnomad AMR exome AF: 0.0125

Gnomad ASJ exome AF: 0.0474

Gnomad EAS exome AF: 0.0337

Gnomad SAS exome AF: 0.0158

Gnomad FIN exome AF: 0.0597

Gnomad NFE exome AF: 0.0552

Gnomad OTH exome AF: 0.0364

GnomAD4 exome AF: 0.0549 AC: 79604 AN: 1449074 Hom.: 2541 Cov.: 32 AF XY: 0.0539 AC XY: 38772 AN XY: 719546

Gnomad4 AFR exome AF: 0.0105

Gnomad4 AMR exome AF: 0.0131

Gnomad4 ASJ exome AF: 0.0471

Gnomad4 EAS exome AF: 0.0217

Gnomad4 SAS exome AF: 0.0175

Gnomad4 FIN exome AF: 0.0601

Gnomad4 NFE exome AF: 0.0623

Gnomad4 OTH exome AF: 0.0508

GnomAD4 genome AF: 0.0408 AC: 6217 AN: 152302 Hom.: 145 Cov.: 32 AF XY: 0.0399 AC XY: 2968 AN XY: 74476

Gnomad4 AFR AF: 0.0133

Gnomad4 AMR AF: 0.0187

Gnomad4 ASJ AF: 0.0499

Gnomad4 EAS AF: 0.0387

Gnomad4 SAS AF: 0.0207

Gnomad4 FIN AF: 0.0582

Gnomad4 NFE AF: 0.0614

Gnomad4 OTH AF: 0.0275

Alfa AF: 0.0466 Hom.: 98

Bravo AF: 0.0360

Asia WGS AF: 0.0270 AC: 93 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

Primary ciliary dyskinesia 33 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.13
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs61734731; hg19: chr16-90106746;