rs12342165

Positions:

• chr9-86947004-T-C

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.-225A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0734 in 301,796 control chromosomes in the GnomAD database, including 886 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.077 (465 hom., cov: 32)
  • Exomes 𝑓: 0.069 (421 hom.)
• Consequence: GAS1 NM_002048.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.05

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=-0.89).
• BP6: Variant 9-86947004-T-C is Benign according to our data. Variant chr9-86947004-T-C is described in ClinVar as [Benign]. Clinvar id is 1275472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAS1	NM_002048.3	c.-225A>G		5_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.-225A>G		5_prime_UTR_variant	1/1		NM_002048.3	ENSP00000298743	P1

Frequencies

GnomAD3 genomes AF: 0.0775 AC: 11740 AN: 151520 Hom.: 464 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.0643

Gnomad ASJ AF: 0.0502

Gnomad EAS AF: 0.000585

Gnomad SAS AF: 0.0374

Gnomad FIN AF: 0.0583

Gnomad MID AF: 0.0513

Gnomad NFE AF: 0.0789

Gnomad OTH AF: 0.0632

GnomAD4 exome AF: 0.0693 AC: 10402 AN: 150168 Hom.: 421 Cov.: 0 AF XY: 0.0690 AC XY: 5329 AN XY: 77234

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.0562

Gnomad4 ASJ exome AF: 0.0556

Gnomad4 EAS exome AF: 0.0000898

Gnomad4 SAS exome AF: 0.0391

Gnomad4 FIN exome AF: 0.0623

Gnomad4 NFE exome AF: 0.0804

Gnomad4 OTH exome AF: 0.0744

GnomAD4 genome AF: 0.0775 AC: 11746 AN: 151628 Hom.: 465 Cov.: 32 AF XY: 0.0770 AC XY: 5706 AN XY: 74092

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.0642

Gnomad4 ASJ AF: 0.0502

Gnomad4 EAS AF: 0.000587

Gnomad4 SAS AF: 0.0372

Gnomad4 FIN AF: 0.0583

Gnomad4 NFE AF: 0.0789

Gnomad4 OTH AF: 0.0626

Alfa AF: 0.0814 Hom.: 316

Bravo AF: 0.0784

Asia WGS AF: 0.0220 AC: 77 AN: 3456

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	clinical testing	GeneDx	Apr 24, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.49

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: rs12342165; hg19: chr9-89561919;