rs3171012

Variant names:

• chr1-67687523-T-C
• rs3171012
• NM_001924.4:c.385-138T>C

Variant summary

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

The NM_001924.4(GADD45A):​c.385-138T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 620,800 control chromosomes in the GnomAD database, including 8,404 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 0.18 (2741 hom., cov: 33)
  • Exomes 𝑓: 0.15 (5663 hom.)
• Consequence: GADD45A NM_001924.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 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.385-138T>C		intron	N/A	NP_001915.1	P24522-1
	GADD45A	NM_001199741.2		c.283-138T>C		intron	N/A	NP_001186670.1	P24522-2
	GADD45A	NM_001199742.2		c.147-138T>C		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.385-138T>C		intron	N/A	ENSP00000360025.4	P24522-1
	GADD45A	ENST00000617962.2	TSL:1	c.331-138T>C		intron	N/A	ENSP00000482814.2	A0A087WZQ0
	GADD45A	ENST00000370985.4	TSL:1	c.283-138T>C		intron	N/A	ENSP00000360024.3	P24522-2

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27469 AN: 152054 Hom.: 2737 Cov.: 33

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.0496

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0290

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.146 AC: 68631 AN: 468630 Hom.: 5663 AF XY: 0.144 AC XY: 35859 AN XY: 248310

African (AFR) AF: 0.248 AC: 3167 AN: 12784

American (AMR) AF: 0.128 AC: 2509 AN: 19610

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 2025 AN: 14198

East Asian (EAS) AF: 0.0269 AC: 842 AN: 31332

South Asian (SAS) AF: 0.108 AC: 4716 AN: 43850

European-Finnish (FIN) AF: 0.228 AC: 7319 AN: 32034

Middle Eastern (MID) AF: 0.192 AC: 386 AN: 2014

European-Non Finnish (NFE) AF: 0.153 AC: 43711 AN: 285986

Other (OTH) AF: 0.147 AC: 3956 AN: 26822

GnomAD4 genome AF: 0.181 AC: 27501 AN: 152170 Hom.: 2741 Cov.: 33 AF XY: 0.182 AC XY: 13552 AN XY: 74398

African (AFR) AF: 0.260 AC: 10772 AN: 41500

American (AMR) AF: 0.134 AC: 2048 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 513 AN: 3472

East Asian (EAS) AF: 0.0289 AC: 150 AN: 5188

South Asian (SAS) AF: 0.110 AC: 530 AN: 4826

European-Finnish (FIN) AF: 0.235 AC: 2489 AN: 10574

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10550 AN: 67998

Other (OTH) AF: 0.161 AC: 340 AN: 2114

Alfa AF: 0.166 Hom.: 724

Bravo AF: 0.176

Asia WGS AF: 0.0960 AC: 335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.29
DANN	Benign	0.57
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3171012; hg19: chr1-68153206;