dbSNP rs3783457: ENSG00000302977:n.68G>T (chr1-67684990-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000790841.1(ENSG00000302977):n.68G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 158,328 control chromosomes in the GnomAD database, including 37 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 0.012 ( 37 hom., cov: 33)

Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

ENSG00000302977
ENST00000790841.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0170

Publications

1 publications found

Variant links:

Genes affected

ENSG00000302977 (HGNC:):

ENSG00000302977 links:

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0123 (1878/152292) while in subpopulation AFR AF = 0.0426 (1772/41566). AF 95% confidence interval is 0.041. There are 37 homozygotes in GnomAd4. There are 905 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 37 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
GADD45A	NM_001924.4 link	c.-505C>A	upstream_gene_variant	ENST00000370986.9	NP_001915.1	P24522-1
GADD45A	NM_001199741.2 link	c.-505C>A	upstream_gene_variant		NP_001186670.1	P24522-2
GADD45A	NM_001199742.2 link	c.-505C>A	upstream_gene_variant		NP_001186671.1	P24522A5JUZ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GADD45A	ENST00000370986.9 link	c.-505C>A		upstream_gene_variant		1	NM_001924.4	ENSP00000360025.4		P24522-1

Frequencies

GnomAD3 genomes

AF:

0.0123

AC:

1871

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0426

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00451

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00716

GnomAD4 exome

AF:

0.000331

AC:

AN:

6036

Hom.:

AF XY:

0.000304

AC XY:

AN XY:

3294

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.0208

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

1604

European-Finnish (FIN)

AF:

0.00

AC:

AN:

220

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

3612

Other (OTH)

AF:

0.00275

AC:

AN:

364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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:

0.0123

AC:

1878

AN:

152292

Hom.:

Cov.:

AF XY:

0.0122

AC XY:

905

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0426

AC:

1772

AN:

41566

American (AMR)

AF:

0.00451

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00174

AC:

AN:

5172

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68018

Other (OTH)

AF:

0.00709

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

178

267

356

445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00605

Hom.:

Bravo

AF:

0.0138

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

4.8

(source)

DANN

Benign

0.52

PhyloP100

0.017

PromoterAI

-0.027

Neutral

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over