chr16-90022496-C-G

Position:

• chr16-90022496-C-G

Variant summary

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

The NM_001286209.2(GAS8):​c.-73+2728C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 470,492 control chromosomes in the GnomAD database, including 45,058 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (11896 hom., cov: 33)
  • Exomes 𝑓: 0.43 (33162 hom.)
• Consequence: GAS8 NM_001286209.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.80

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=-0.81).
• BP6: Variant 16-90022496-C-G is Benign according to our data. Variant chr16-90022496-C-G is described in ClinVar as [Benign]. Clinvar id is 1294084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAS8	NM_001286209.2	c.-73+2728C>G		intron_variant			NP_001273138.1
GAS8	XM_011522992.3	c.-269+2728C>G		intron_variant			XP_011521294.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAS8	ENST00000536122.7	c.-73+2728C>G		intron_variant		2		ENSP00000440977	A1
GAS8	ENST00000561675.1	c.-269+2728C>G		intron_variant		3		ENSP00000457554
GAS8	ENST00000564392.5	c.-73+290C>G		intron_variant		3		ENSP00000455172

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55919 AN: 152086 Hom.: 11888 Cov.: 33

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.384

GnomAD4 exome AF: 0.433 AC: 137722 AN: 318286 Hom.: 33162 AF XY: 0.433 AC XY: 72248 AN XY: 166684

Gnomad4 AFR exome AF: 0.189

Gnomad4 AMR exome AF: 0.536

Gnomad4 ASJ exome AF: 0.282

Gnomad4 EAS exome AF: 0.851

Gnomad4 SAS exome AF: 0.520

Gnomad4 FIN exome AF: 0.531

Gnomad4 NFE exome AF: 0.377

Gnomad4 OTH exome AF: 0.403

GnomAD4 genome AF: 0.368 AC: 55953 AN: 152206 Hom.: 11896 Cov.: 33 AF XY: 0.384 AC XY: 28540 AN XY: 74408

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.783

Gnomad4 SAS AF: 0.530

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.388

Alfa AF: 0.365 Hom.: 1355

Bravo AF: 0.354

Asia WGS AF: 0.608 AC: 2116 AN: 3478

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	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2241038; hg19: chr16-90088904;