chr1-67686297-T-G

Variant names:

• chr1-67686297-T-G
• rs2759219
• NM_001924.4:c.147-53T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001924.4(GADD45A):​c.147-53T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 1,539,056 control chromosomes in the GnomAD database, including 547,885 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 0.80 (49699 hom., cov: 34)
  • Exomes 𝑓: 0.85 (498186 hom.)
• Consequence: GADD45A NM_001924.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.968
• Publications: 8 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GADD45A	NM_001924.4	MANE Select	c.147-53T>G		intron	N/A	NP_001915.1	P24522-1
	GADD45A	NM_001199741.2		c.45-53T>G		intron	N/A	NP_001186670.1	P24522-2
	GADD45A	NM_001199742.2		c.146+171T>G		intron	N/A	NP_001186671.1	A5JUZ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GADD45A	ENST00000370986.9	TSL:1 MANE Select	c.147-53T>G		intron	N/A	ENSP00000360025.4	P24522-1
	GADD45A	ENST00000617962.2	TSL:1	c.147-107T>G		intron	N/A	ENSP00000482814.2	A0A087WZQ0
	GADD45A	ENST00000370985.4	TSL:1	c.45-53T>G		intron	N/A	ENSP00000360024.3	P24522-2

Frequencies

GnomAD3 genomes AF: 0.803 AC: 122094 AN: 152054 Hom.: 49658 Cov.: 34

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.768

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.812

GnomAD4 exome AF: 0.846 AC: 1172987 AN: 1386884 Hom.: 498186 Cov.: 23 AF XY: 0.846 AC XY: 581315 AN XY: 687158

African (AFR) AF: 0.676 AC: 21311 AN: 31548

American (AMR) AF: 0.860 AC: 33510 AN: 38970

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 20308 AN: 24410

East Asian (EAS) AF: 0.602 AC: 22949 AN: 38112

South Asian (SAS) AF: 0.844 AC: 69086 AN: 81820

European-Finnish (FIN) AF: 0.926 AC: 46162 AN: 49876

Middle Eastern (MID) AF: 0.774 AC: 3914 AN: 5056

European-Non Finnish (NFE) AF: 0.857 AC: 908353 AN: 1059910

Other (OTH) AF: 0.829 AC: 47394 AN: 57182

GnomAD4 genome AF: 0.803 AC: 122194 AN: 152172 Hom.: 49699 Cov.: 34 AF XY: 0.804 AC XY: 59843 AN XY: 74406

African (AFR) AF: 0.685 AC: 28453 AN: 41514

American (AMR) AF: 0.814 AC: 12455 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.829 AC: 2878 AN: 3472

East Asian (EAS) AF: 0.616 AC: 3167 AN: 5138

South Asian (SAS) AF: 0.830 AC: 4007 AN: 4830

European-Finnish (FIN) AF: 0.932 AC: 9897 AN: 10614

Middle Eastern (MID) AF: 0.767 AC: 224 AN: 292

European-Non Finnish (NFE) AF: 0.862 AC: 58597 AN: 67988

Other (OTH) AF: 0.814 AC: 1719 AN: 2112

Alfa AF: 0.841 Hom.: 6782

Bravo AF: 0.786

Asia WGS AF: 0.746 AC: 2597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	9.9
DANN	Benign	0.36
PhyloP100		0.97
Mutation Taster		=100/0	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: rs2759219; hg19: chr1-68151980; COSMIC: COSV63974744;