16-90022905-C-T

Position:

• chr16-90022905-C-T

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.3+181C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0678 in 152,224 control chromosomes in the GnomAD database, including 1,055 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.068 (1055 hom., cov: 33)
• Consequence: GAS8 NM_001481.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.45

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=-0.91).
• BP6: Variant 16-90022905-C-T is Benign according to our data. Variant chr16-90022905-C-T is described in ClinVar as [Benign]. Clinvar id is 1286845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAS8	NM_001481.3	c.3+181C>T		intron_variant		ENST00000268699.9	NP_001472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAS8	ENST00000268699.9	c.3+181C>T		intron_variant		1	NM_001481.3	ENSP00000268699	P4

Frequencies

GnomAD3 genomes AF: 0.0677 AC: 10304 AN: 152106 Hom.: 1057 Cov.: 33

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0312

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0257

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00559

Gnomad OTH AF: 0.0498

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0678 AC: 10317 AN: 152224 Hom.: 1055 Cov.: 33 AF XY: 0.0651 AC XY: 4846 AN XY: 74430

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.0312

Gnomad4 ASJ AF: 0.0277

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0255

Gnomad4 FIN AF: 0.00273

Gnomad4 NFE AF: 0.00559

Gnomad4 OTH AF: 0.0493

Alfa AF: 0.00360 Hom.: 1

Bravo AF: 0.0749

Asia WGS AF: 0.0280 AC: 97 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.91
CADD	Benign	2.4
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs58490907; hg19: chr16-90089313;