rs868045

chr16-90036427-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001481.3(GAS8):c.597A>G(p.Glu199=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 1,611,578 control chromosomes in the GnomAD database, including 125,276 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10512 hom., cov: 33)
  • Exomes 𝑓: 0.39 (114764 hom.)
• Consequence: GAS8 NM_001481.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 3.00

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 16-90036427-A-G is Benign according to our data. Variant chr16-90036427-A-G is described in ClinVar as [Benign]. Clinvar id is 402891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAS8	NM_001481.3	c.597A>G	p.Glu199=	synonymous_variant	6/11	ENST00000268699.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAS8	ENST00000268699.9	c.597A>G	p.Glu199=	synonymous_variant	6/11	1	NM_001481.3	P4

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54756 AN: 152016 Hom.: 10501 Cov.: 33

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.0154

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.374

GnomAD3 exomes AF: 0.320 AC: 80201 AN: 250594 Hom.: 14763 AF XY: 0.325 AC XY: 43984 AN XY: 135434

Gnomad AFR exome AF: 0.384

Gnomad AMR exome AF: 0.209

Gnomad ASJ exome AF: 0.492

Gnomad EAS exome AF: 0.00832

Gnomad SAS exome AF: 0.277

Gnomad FIN exome AF: 0.288

Gnomad NFE exome AF: 0.396

Gnomad OTH exome AF: 0.351

GnomAD4 exome AF: 0.386 AC: 563155 AN: 1459444 Hom.: 114764 Cov.: 43 AF XY: 0.384 AC XY: 278481 AN XY: 725566

Gnomad4 AFR exome AF: 0.373

Gnomad4 AMR exome AF: 0.219

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.0148

Gnomad4 SAS exome AF: 0.278

Gnomad4 FIN exome AF: 0.287

Gnomad4 NFE exome AF: 0.417

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.360 AC: 54803 AN: 152134 Hom.: 10512 Cov.: 33 AF XY: 0.350 AC XY: 26060 AN XY: 74382

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.0154

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.371

Alfa AF: 0.399 Hom.: 24398

Bravo AF: 0.364

Asia WGS AF: 0.157 AC: 547 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia 33 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

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	-0.62
Cadd	Benign	3.6
Dann	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs868045; hg19: chr16-90102835; COSMIC: COSV51943445; COSMIC: COSV51943445;