Variant chr1-67686488-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001924.4(GADD45A):c.285G>A(p.Pro95=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00399 in 1,613,512 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 1 hom., cov: 34)

Exomes 𝑓: 0.0041 ( 21 hom. )

Consequence

GADD45A
NM_001924.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.689

Variant links:

Genes affected

GADD45A (HGNC:4095): (growth arrest and DNA damage inducible alpha) This gene is a member of a group of genes whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. The protein encoded by this gene responds to environmental stresses by mediating activation of the p38/JNK pathway via MTK1/MEKK4 kinase. The DNA damage-induced transcription of this gene is mediated by both p53-dependent and -independent mechanisms. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.[provided by RefSeq, Dec 2010]

GADD45A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 1-67686488-G-A is Benign according to our data. Variant chr1-67686488-G-A is described in ClinVar as [Benign]. Clinvar id is 784441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.689 with no splicing effect.

BS2

High AC in GnomAd4 at 519 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GADD45A	NM_001924.4 linkuse as main transcript	c.285G>A	p.Pro95=	synonymous_variant	3/4	ENST00000370986.9	NP_001915.1
GADD45A	NM_001199741.2 linkuse as main transcript	c.183G>A	p.Pro61=	synonymous_variant	2/3		NP_001186670.1
GADD45A	NM_001199742.2 linkuse as main transcript	c.146+362G>A		intron_variant			NP_001186671.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GADD45A	ENST00000370986.9 linkuse as main transcript	c.285G>A	p.Pro95=	synonymous_variant	3/4	1	NM_001924.4	ENSP00000360025	P1	P24522-1

Frequencies

GnomAD3 genomes

AF:

0.00341

AC:

519

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000844

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00868

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00494

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00413

AC:

1031

AN:

249652

Hom.:

AF XY:

0.00462

AC XY:

625

AN XY:

135358

show subpopulations

Gnomad AFR exome

AF:

0.000251

Gnomad AMR exome

AF:

0.00214

Gnomad ASJ exome

AF:

0.0108

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00820

Gnomad FIN exome

AF:

0.00102

Gnomad NFE exome

AF:

0.00479

Gnomad OTH exome

AF:

0.00524

GnomAD4 exome

AF:

0.00405

AC:

5922

AN:

1461134

Hom.:

Cov.:

AF XY:

0.00426

AC XY:

3099

AN XY:

726914

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

Gnomad4 AMR exome

AF:

0.00212

Gnomad4 ASJ exome

AF:

0.0117

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00825

Gnomad4 FIN exome

AF:

0.00100

Gnomad4 NFE exome

AF:

0.00401

Gnomad4 OTH exome

AF:

0.00407

GnomAD4 genome

AF:

0.00341

AC:

519

AN:

152378

Hom.:

Cov.:

AF XY:

0.00311

AC XY:

232

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.000841

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.0124

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00869

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00494

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00521

Hom.:

Bravo

AF:

0.00333

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.00583

EpiControl

AF:

0.00605

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Labcorp Genetics (formerly Invitae), Labcorp	Apr 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

7.3

DANN

Benign

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over