NM_002048.3:c.-225A>G

Variant names:

• chr9-86947004-T-C
• rs12342165
• NM_002048.3:c.-225A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

GAS1 Gene-Disease associations (from GenCC):

• holoprosencephaly

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002048.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS1	NM_002048.3	MANE Select	c.-225A>G		5_prime_UTR	Exon 1 of 1	NP_002039.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS1	ENST00000298743.9	TSL:6 MANE Select	c.-225A>G		5_prime_UTR	Exon 1 of 1	ENSP00000298743.7

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

African (AFR) AF: 0.101 AC: 357 AN: 3526

American (AMR) AF: 0.0562 AC: 217 AN: 3864

Ashkenazi Jewish (ASJ) AF: 0.0556 AC: 259 AN: 4658

East Asian (EAS) AF: 0.0000898 AC: 1 AN: 11138

South Asian (SAS) AF: 0.0391 AC: 58 AN: 1484

European-Finnish (FIN) AF: 0.0623 AC: 1709 AN: 27434

Middle Eastern (MID) AF: 0.0390 AC: 27 AN: 692

European-Non Finnish (NFE) AF: 0.0804 AC: 7127 AN: 88676

Other (OTH) AF: 0.0744 AC: 647 AN: 8696

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

African (AFR) AF: 0.104 AC: 4298 AN: 41412

American (AMR) AF: 0.0642 AC: 979 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0502 AC: 174 AN: 3468

East Asian (EAS) AF: 0.000587 AC: 3 AN: 5112

South Asian (SAS) AF: 0.0372 AC: 179 AN: 4810

European-Finnish (FIN) AF: 0.0583 AC: 610 AN: 10456

Middle Eastern (MID) AF: 0.0552 AC: 16 AN: 290

European-Non Finnish (NFE) AF: 0.0789 AC: 5351 AN: 67824

Other (OTH) AF: 0.0626 AC: 131 AN: 2094

Alfa AF: 0.0805 Hom.: 421

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Apr 24, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.49
PhyloP100		-1.0
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12342165; hg19: chr9-89561919;