16-90022715-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001481.3(GAS8):c.-7T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00776 in 1,417,528 control chromosomes in the GnomAD database, including 555 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (329 hom., cov: 33)
  • Exomes 𝑓: 0.0043 (226 hom.)
• Consequence: GAS8 NM_001481.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.338

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-90022715-T-G is Benign according to our data. Variant chr16-90022715-T-G is described in ClinVar as [Benign]. Clinvar id is 1236662.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAS8	NM_001481.3	c.-7T>G		5_prime_UTR_variant	1/11	ENST00000268699.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAS8	ENST00000268699.9	c.-7T>G		5_prime_UTR_variant	1/11	1	NM_001481.3	P4

Frequencies

GnomAD3 genomes AF: 0.0366 AC: 5563 AN: 151912 Hom.: 329 Cov.: 33

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0160

Gnomad ASJ AF: 0.00289

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00498

Gnomad FIN AF: 0.0000948

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00135

Gnomad OTH AF: 0.0187

GnomAD3 exomes AF: 0.00489 AC: 329 AN: 67332 Hom.: 6 AF XY: 0.00462 AC XY: 179 AN XY: 38758

Gnomad AFR exome AF: 0.0808

Gnomad AMR exome AF: 0.00668

Gnomad ASJ exome AF: 0.00219

Gnomad EAS exome AF: 0.00181

Gnomad SAS exome AF: 0.00515

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000950

Gnomad OTH exome AF: 0.00444

GnomAD4 exome AF: 0.00429 AC: 5432 AN: 1265500 Hom.: 226 Cov.: 31 AF XY: 0.00411 AC XY: 2542 AN XY: 618122

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.00833

Gnomad4 ASJ exome AF: 0.00246

Gnomad4 EAS exome AF: 0.000105

Gnomad4 SAS exome AF: 0.00566

Gnomad4 FIN exome AF: 0.000227

Gnomad4 NFE exome AF: 0.00109

Gnomad4 OTH exome AF: 0.00932

GnomAD4 genome AF: 0.0366 AC: 5568 AN: 152028 Hom.: 329 Cov.: 33 AF XY: 0.0353 AC XY: 2622 AN XY: 74332

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.0160

Gnomad4 ASJ AF: 0.00289

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.00499

Gnomad4 FIN AF: 0.0000948

Gnomad4 NFE AF: 0.00135

Gnomad4 OTH AF: 0.0185

Alfa AF: 0.00181 Hom.: 4

Bravo AF: 0.0401

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia 33 Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 22, 2023

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.99
Dann	Benign	0.49

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: rs80287915; hg19: chr16-90089123;