9-86945534-G-A

Position:

• chr9-86945534-G-A

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.*208C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0387 in 431,430 control chromosomes in the GnomAD database, including 429 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (240 hom., cov: 32)
  • Exomes 𝑓: 0.033 (189 hom.)
• Consequence: GAS1 NM_002048.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.06

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=-0.62).
• BP6: Variant 9-86945534-G-A is Benign according to our data. Variant chr9-86945534-G-A is described in ClinVar as [Benign]. Clinvar id is 1270943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAS1	NM_002048.3	c.*208C>T		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.*208C>T		3_prime_UTR_variant	1/1	6	NM_002048.3	ENSP00000298743.7

Frequencies

GnomAD3 genomes AF: 0.0486 AC: 7400 AN: 152170 Hom.: 238 Cov.: 32

Gnomad AFR AF: 0.0766

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0609

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.0352

Gnomad FIN AF: 0.0481

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0354

Gnomad OTH AF: 0.0449

GnomAD4 exome AF: 0.0333 AC: 9282 AN: 279142 Hom.: 189 Cov.: 4 AF XY: 0.0332 AC XY: 4803 AN XY: 144672

Gnomad4 AFR exome AF: 0.0792

Gnomad4 AMR exome AF: 0.0739

Gnomad4 ASJ exome AF: 0.0203

Gnomad4 EAS exome AF: 0.00170

Gnomad4 SAS exome AF: 0.0336

Gnomad4 FIN exome AF: 0.0456

Gnomad4 NFE exome AF: 0.0324

Gnomad4 OTH exome AF: 0.0353

GnomAD4 genome AF: 0.0487 AC: 7412 AN: 152288 Hom.: 240 Cov.: 32 AF XY: 0.0500 AC XY: 3725 AN XY: 74452

Gnomad4 AFR AF: 0.0766

Gnomad4 AMR AF: 0.0612

Gnomad4 ASJ AF: 0.0256

Gnomad4 EAS AF: 0.000967

Gnomad4 SAS AF: 0.0348

Gnomad4 FIN AF: 0.0481

Gnomad4 NFE AF: 0.0354

Gnomad4 OTH AF: 0.0445

Alfa AF: 0.0452 Hom.: 36

Bravo AF: 0.0493

Asia WGS AF: 0.0230 AC: 79 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	Apr 12, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	8.5
DANN	Benign	0.93

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: rs112023786; hg19: chr9-89560449;