9-86945528-C-G

Position:

• chr9-86945528-C-G

Variant summary

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

The NM_002048.3(GAS1):​c.*214G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0435 in 420,190 control chromosomes in the GnomAD database, including 596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (391 hom., cov: 32)
  • Exomes 𝑓: 0.035 (205 hom.)
• Consequence: GAS1 NM_002048.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.954

Genes affected

GAS1 (HGNC:4165): (growth arrest specific 1) Growth arrest-specific 1 plays a role in growth suppression. GAS1 blocks entry to S phase and prevents cycling of normal and transformed cells. Gas1 is a putative tumor suppressor gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 9-86945528-C-G is Benign according to our data. Variant chr9-86945528-C-G is described in ClinVar as [Benign]. Clinvar id is 1236851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAS1	NM_002048.3	c.*214G>C		3_prime_UTR_variant	1/1	ENST00000298743.9	NP_002039.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAS1	ENST00000298743.9	c.*214G>C		3_prime_UTR_variant	1/1	6	NM_002048.3	ENSP00000298743.7

Frequencies

GnomAD3 genomes AF: 0.0586 AC: 8918 AN: 152094 Hom.: 384 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0654

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.000967

Gnomad SAS AF: 0.0358

Gnomad FIN AF: 0.0482

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0355

Gnomad OTH AF: 0.0531

GnomAD4 exome AF: 0.0347 AC: 9310 AN: 267978 Hom.: 205 Cov.: 4 AF XY: 0.0346 AC XY: 4813 AN XY: 139026

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.0785

Gnomad4 ASJ exome AF: 0.0202

Gnomad4 EAS exome AF: 0.00168

Gnomad4 SAS exome AF: 0.0344

Gnomad4 FIN exome AF: 0.0459

Gnomad4 NFE exome AF: 0.0328

Gnomad4 OTH exome AF: 0.0392

GnomAD4 genome AF: 0.0588 AC: 8952 AN: 152212 Hom.: 391 Cov.: 32 AF XY: 0.0601 AC XY: 4474 AN XY: 74416

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.0656

Gnomad4 ASJ AF: 0.0256

Gnomad4 EAS AF: 0.000970

Gnomad4 SAS AF: 0.0354

Gnomad4 FIN AF: 0.0482

Gnomad4 NFE AF: 0.0355

Gnomad4 OTH AF: 0.0526

Alfa AF: 0.0229 Hom.: 16

Bravo AF: 0.0609

Asia WGS AF: 0.0260 AC: 91 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	Dec 22, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Benign	0.85

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: rs113149366; hg19: chr9-89560443;