Genetic Variant GADD45A:c.-247T>G (chr1-67685248-T-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001924.4(GADD45A):c.-247T>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 0.000701 in 501,814 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0017 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

GADD45A
NM_001924.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.48

Publications

2 publications found

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:

ENSG00000302977 (HGNC:):

ENSG00000302977 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BS2

High AC in GnomAd4 at 264 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001924.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GADD45A	NM_001924.4	MANE Select	c.-247T>G	5_prime_UTR	Exon 1 of 4	NP_001915.1
GADD45A	NM_001199741.2		c.-247T>G	5_prime_UTR	Exon 1 of 3	NP_001186670.1
GADD45A	NM_001199742.2		c.-247T>G	5_prime_UTR	Exon 1 of 3	NP_001186671.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GADD45A	ENST00000370986.9	TSL:1 MANE Select	c.-247T>G	5_prime_UTR	Exon 1 of 4	ENSP00000360025.4
GADD45A	ENST00000370985.4	TSL:1	c.-247T>G	5_prime_UTR	Exon 1 of 3	ENSP00000360024.3
GADD45A	ENST00000460575.1	TSL:2	n.20T>G	non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.00174

AC:

264

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00609

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00191

GnomAD4 exome

AF:

0.000252

AC:

AN:

349618

Hom.:

Cov.:

AF XY:

0.000182

AC XY:

AN XY:

186586

show subpopulations

African (AFR)

AF:

0.00767

AC:

AN:

6912

American (AMR)

AF:

0.000618

AC:

AN:

8088

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10542

East Asian (EAS)

AF:

0.00

AC:

AN:

22182

South Asian (SAS)

AF:

0.0000294

AC:

AN:

33966

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26904

Middle Eastern (MID)

AF:

0.000615

AC:

AN:

1626

European-Non Finnish (NFE)

AF:

0.0000686

AC:

AN:

218516

Other (OTH)

AF:

0.000623

AC:

AN:

20882

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00173

AC:

264

AN:

152196

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

132

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.00609

AC:

253

AN:

41524

American (AMR)

AF:

0.000392

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67986

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00205

Hom.:

Bravo

AF:

0.00219

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.7

(source)

DANN

Benign

0.64

PhyloP100

-2.5

PromoterAI

-0.068

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over