16-90027561-T-C

Variant summary

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

The NM_001481.3(GAS8):c.4-75T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 1,457,834 control chromosomes in the GnomAD database, including 196,524 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.54 (22760 hom., cov: 32)
  • Exomes 𝑓: 0.50 (173764 hom.)
• Consequence: GAS8 NM_001481.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.195

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 16-90027561-T-C is Benign according to our data. Variant chr16-90027561-T-C is described in ClinVar as [Benign]. Clinvar id is 1223279.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAS8	NM_001481.3	c.4-75T>C		intron_variant		ENST00000268699.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAS8	ENST00000268699.9	c.4-75T>C		intron_variant		1	NM_001481.3	P4

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81558 AN: 152014 Hom.: 22721 Cov.: 32

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.522

GnomAD4 exome AF: 0.503 AC: 656492 AN: 1305702 Hom.: 173764 AF XY: 0.504 AC XY: 331063 AN XY: 656848

Gnomad4 AFR exome AF: 0.525

Gnomad4 AMR exome AF: 0.729

Gnomad4 ASJ exome AF: 0.347

Gnomad4 EAS exome AF: 0.967

Gnomad4 SAS exome AF: 0.596

Gnomad4 FIN exome AF: 0.626

Gnomad4 NFE exome AF: 0.462

Gnomad4 OTH exome AF: 0.515

GnomAD4 genome AF: 0.537 AC: 81654 AN: 152132 Hom.: 22760 Cov.: 32 AF XY: 0.550 AC XY: 40883 AN XY: 74378

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.954

Gnomad4 SAS AF: 0.607

Gnomad4 FIN AF: 0.637

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.524

Alfa AF: 0.487 Hom.: 30994

Bravo AF: 0.537

Asia WGS AF: 0.747 AC: 2597 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	2.4
Dann	Benign	0.61

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: rs3743829; hg19: chr16-90093969;