rs148760410

Positions:

• chr16-90032836-G-C

Variant summary

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

The NM_001286208.2(GAS8):​c.-115G>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000768 in 1,613,970 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00090 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00075 (9 hom.)
• Consequence: GAS8 NM_001286208.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.582

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]

GAS8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00311625).
• BP6: Variant 16-90032836-G-C is Benign according to our data. Variant chr16-90032836-G-C is described in ClinVar as [Benign]. Clinvar id is 542271.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0009 (137/152194) while in subpopulation EAS AF= 0.0189 (98/5188). AF 95% confidence interval is 0.0159. There are 0 homozygotes in gnomad4. There are 69 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAS8	NM_001481.3	c.407G>C	p.Ser136Thr	missense_variant	4/11	ENST00000268699.9	NP_001472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAS8	ENST00000268699.9	c.407G>C	p.Ser136Thr	missense_variant	4/11	1	NM_001481.3	ENSP00000268699.4

Frequencies

GnomAD3 genomes AF: 0.000894 AC: 136 AN: 152076 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0187

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00176 AC: 443 AN: 251324 Hom.: 0 AF XY: 0.00163 AC XY: 221 AN XY: 135854

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.0199

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000378

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.000754 AC: 1102 AN: 1461776 Hom.: 9 Cov.: 33 AF XY: 0.000755 AC XY: 549 AN XY: 727208

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000201

Gnomad4 ASJ exome AF: 0.000344

Gnomad4 EAS exome AF: 0.0150

Gnomad4 SAS exome AF: 0.000336

Gnomad4 FIN exome AF: 0.000356

Gnomad4 NFE exome AF: 0.000237

Gnomad4 OTH exome AF: 0.00291

GnomAD4 genome AF: 0.000900 AC: 137 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.000927 AC XY: 69 AN XY: 74404

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000850

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.0189

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.000305 Hom.: 0

Bravo AF: 0.00110

ExAC AF: 0.00194 AC: 236

Asia WGS AF: 0.0120 AC: 40 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

GAS8-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 12, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Primary ciliary dyskinesia 33 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.8
DANN	Benign	0.51
DEOGEN2	Benign	0.0052	.;.;T;T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.15	T;T;T;T
MetaRNN	Benign	0.0031	T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.90	N;N;N;.
REVEL	Benign	0.022
Sift	Benign	0.60	T;T;T;.
Sift4G	Benign	0.55	T;T;T;T
Polyphen		0.0	.;.;B;.
Vest4		0.19
MVP		0.30
MPC		0.017
ClinPred		0.0063	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.040
gMVP		0.036

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: rs148760410; hg19: chr16-90099244;