16-90029265-C-T

Variant names:

• chr16-90029265-C-T
• rs141306543
• NM_001481.3:c.90+1543C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001481.3(GAS8):​c.90+1543C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00993 in 1,365,616 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0072 (7 hom., cov: 33)
  • Exomes 𝑓: 0.010 (92 hom.)
• Consequence: GAS8 NM_001481.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.01

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]

GAS8-AS1 (HGNC:1197): (GAS8 antisense RNA 1) This gene encodes a long non-coding RNA (lncRNA) that may function as a tumor suppressor. Mutations in this gene have been identified in human papillary thyroid carcinoma (PTC) patients that abrogate the ability of encoded lncRNA to inhibit cancer cell growth. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 16-90029265-C-T is Benign according to our data. Variant chr16-90029265-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3024804.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00716 (1084/151310) while in subpopulation NFE AF= 0.0106 (717/67908). AF 95% confidence interval is 0.00992. There are 7 homozygotes in gnomad4. There are 474 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAS8	NM_001481.3	c.90+1543C>T		intron_variant	Intron 2 of 10	ENST00000268699.9	NP_001472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAS8	ENST00000268699.9	c.90+1543C>T		intron_variant	Intron 2 of 10	1	NM_001481.3	ENSP00000268699.4

Frequencies

GnomAD3 genomes AF: 0.00716 AC: 1083 AN: 151196 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00355

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00903

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00458

Gnomad FIN AF: 0.00295

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.00817

GnomAD3 exomes AF: 0.00626 AC: 1532 AN: 244656 Hom.: 2 AF XY: 0.00655 AC XY: 873 AN XY: 133196

Gnomad AFR exome AF: 0.00314

Gnomad AMR exome AF: 0.00611

Gnomad ASJ exome AF: 0.00281

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00386

Gnomad FIN exome AF: 0.00265

Gnomad NFE exome AF: 0.00934

Gnomad OTH exome AF: 0.00812

GnomAD4 exome AF: 0.0103 AC: 12478 AN: 1214306 Hom.: 92 Cov.: 32 AF XY: 0.0100 AC XY: 6021 AN XY: 601848

Gnomad4 AFR exome AF: 0.00455

Gnomad4 AMR exome AF: 0.00645

Gnomad4 ASJ exome AF: 0.00308

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00323

Gnomad4 FIN exome AF: 0.00295

Gnomad4 NFE exome AF: 0.0117

Gnomad4 OTH exome AF: 0.0110

GnomAD4 genome AF: 0.00716 AC: 1084 AN: 151310 Hom.: 7 Cov.: 33 AF XY: 0.00641 AC XY: 474 AN XY: 73918

Gnomad4 AFR AF: 0.00354

Gnomad4 AMR AF: 0.00902

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00479

Gnomad4 FIN AF: 0.00295

Gnomad4 NFE AF: 0.0106

Gnomad4 OTH AF: 0.00809

Alfa AF: 0.00818 Hom.: 3

Bravo AF: 0.00691

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.0114

EpiControl AF: 0.00937

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

GAS8-AS1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs141306543; hg19: chr16-90095673;