dbSNP rs12342165: GAS1:c.-225A>G (chr9-86947004-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.05

Publications

8 publications found

Variant links:

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

GAS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAS1	NM_002048.3 link	c.-225A>G		5_prime_UTR_variant	Exon 1 of 1	ENST00000298743.9	NP_002039.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAS1	ENST00000298743.9 link	c.-225A>G		5_prime_UTR_variant	Exon 1 of 1	6	NM_002048.3	ENSP00000298743.7

Frequencies

GnomAD3 genomes

AF:

0.0775

AC:

11740

AN:

151520

Hom.:

464

Cov.:

show subpopulations

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.:

AF XY:

0.0690

AC XY:

5329

AN XY:

77234

show subpopulations

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:

AN:

11138

South Asian (SAS)

AF:

0.0391

AC:

AN:

1484

European-Finnish (FIN)

AF:

0.0623

AC:

1709

AN:

27434

Middle Eastern (MID)

AF:

0.0390

AC:

AN:

692

European-Non Finnish (NFE)

AF:

0.0804

AC:

7127

AN:

88676

Other (OTH)

AF:

0.0744

AC:

647

AN:

8696

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

462

925

1387

1850

2312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0775

AC:

11746

AN:

151628

Hom.:

465

Cov.:

AF XY:

0.0770

AC XY:

5706

AN XY:

74092

show subpopulations

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:

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:

AN:

290

European-Non Finnish (NFE)

AF:

0.0789

AC:

5351

AN:

67824

Other (OTH)

AF:

0.0626

AC:

131

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

556

1111

1667

2222

2778

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

130

260

390

520

650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0805

Hom.:

421

Bravo

AF:

0.0784

Asia WGS

AF:

0.0220

AC:

AN:

3456

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.0

(source)

DANN

Benign

0.49

PhyloP100

-1.0

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over