16-90022927-C-T

Position:

• chr16-90022927-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+203C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,158 control chromosomes in the GnomAD database, including 2,543 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.14 (2543 hom., cov: 33)
• Consequence: GAS8 NM_001481.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.353

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=-0.84).
• BP6: Variant 16-90022927-C-T is Benign according to our data. Variant chr16-90022927-C-T is described in ClinVar as [Benign]. Clinvar id is 1221064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAS8	NM_001481.3	c.3+203C>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+203C>T		intron_variant		1	NM_001481.3	ENSP00000268699	P4

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21658 AN: 152040 Hom.: 2532 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.0611

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0936

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.142 AC: 21682 AN: 152158 Hom.: 2543 Cov.: 33 AF XY: 0.157 AC XY: 11666 AN XY: 74370

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.0611

Gnomad4 EAS AF: 0.624

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.0936

Gnomad4 OTH AF: 0.122

Alfa AF: 0.0483 Hom.: 46

Bravo AF: 0.141

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	-0.84
CADD	Benign	9.6
DANN	Benign	0.95

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: rs59443037; hg19: chr16-90089335;