16-90027670-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001481.3(GAS8):c.38A>G(p.Lys13Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0019 in 1,614,190 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (28 hom., cov: 33)
  • Exomes 𝑓: 0.0010 (27 hom.)
• Consequence: GAS8 NM_001481.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.94

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 (MetaRNN=0.004105091).
• BP6: Variant 16-90027670-A-G is Benign according to our data. Variant chr16-90027670-A-G is described in ClinVar as [Benign]. Clinvar id is 475564.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1597/152358) while in subpopulation AFR AF= 0.0371 (1544/41586). AF 95% confidence interval is 0.0356. There are 28 homozygotes in gnomad4. There are 737 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAS8	NM_001481.3	c.38A>G	p.Lys13Arg	missense_variant	2/11	ENST00000268699.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAS8	ENST00000268699.9	c.38A>G	p.Lys13Arg	missense_variant	2/11	1	NM_001481.3	P4

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1599 AN: 152240 Hom.: 28 Cov.: 33

Gnomad AFR AF: 0.0373

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00248

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00267 AC: 672 AN: 251432 Hom.: 11 AF XY: 0.00196 AC XY: 267 AN XY: 135898

Gnomad AFR exome AF: 0.0387

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.00101 AC: 1471 AN: 1461832 Hom.: 27 Cov.: 32 AF XY: 0.000861 AC XY: 626 AN XY: 727216

Gnomad4 AFR exome AF: 0.0383

Gnomad4 AMR exome AF: 0.00101

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000153

Gnomad4 OTH exome AF: 0.00190

GnomAD4 genome AF: 0.0105 AC: 1597 AN: 152358 Hom.: 28 Cov.: 33 AF XY: 0.00989 AC XY: 737 AN XY: 74520

Gnomad4 AFR AF: 0.0371

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00181 Hom.: 6

Bravo AF: 0.0121

ESP6500AA AF: 0.0348 AC: 153

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00324 AC: 393

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia 33 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	17
Dann	Benign	0.92
DEOGEN2	Benign	0.012	T
Eigen	Benign	0.087
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.099
Sift	Benign	0.23	T
Sift4G	Benign	0.31	T
Polyphen		0.35	B
Vest4		0.29
MVP		0.67
MPC		0.017
ClinPred		0.020	T
GERP RS		5.5
Varity_R		0.11
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs61734732; hg19: chr16-90094078; COSMIC: COSV99064917; COSMIC: COSV99064917;