16-90022379-G-A

Variant summary

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

The NM_001286209.2(GAS8):c.-73+2611G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,218 control chromosomes in the GnomAD database, including 2,849 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (2849 hom., cov: 33)
• Consequence: GAS8 NM_001286209.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.45

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 16-90022379-G-A is Benign according to our data. Variant chr16-90022379-G-A is described in ClinVar as [Benign]. Clinvar id is 1269255.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAS8	NM_001286209.2	c.-73+2611G>A		intron_variant
GAS8	XM_011522992.3	c.-269+2611G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAS8	ENST00000536122.7	c.-73+2611G>A		intron_variant		2		A1
GAS8	ENST00000561675.1	c.-269+2611G>A		intron_variant		3
GAS8	ENST00000564392.5	c.-73+173G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23536 AN: 152102 Hom.: 2836 Cov.: 33

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.0600

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0772

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.155 AC: 23586 AN: 152218 Hom.: 2849 Cov.: 33 AF XY: 0.168 AC XY: 12533 AN XY: 74414

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.0600

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.0772

Gnomad4 OTH AF: 0.121

Alfa AF: 0.0698 Hom.: 124

Bravo AF: 0.157

Asia WGS AF: 0.333 AC: 1162 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.48
Dann	Benign	0.78

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs872010; hg19: chr16-90088787;