chr19-2477825-T-C

Position:

• chr19-2477825-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015675.4(GADD45B):​c.*224T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 382,384 control chromosomes in the GnomAD database, including 2,266 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 0.11 (952 hom., cov: 31)
  • Exomes 𝑓: 0.098 (1314 hom.)
• Consequence: GADD45B NM_015675.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.449

Genes affected

GADD45B (HGNC:4096): (growth arrest and DNA damage inducible beta) 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 genes in this group respond to environmental stresses by mediating activation of the p38/JNK pathway. This activation is mediated via their proteins binding and activating MTK1/MEKK4 kinase, which is an upstream activator of both p38 and JNK MAPKs. The function of these genes or their protein products is involved in the regulation of growth and apoptosis. These genes are regulated by different mechanisms, but they are often coordinately expressed and can function cooperatively in inhibiting cell growth. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GADD45B	NM_015675.4	c.*224T>C		3_prime_UTR_variant	4/4	ENST00000215631.9	NP_056490.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GADD45B	ENST00000215631.9	c.*224T>C		3_prime_UTR_variant	4/4	1	NM_015675.4	ENSP00000215631	P1
GADD45B	ENST00000592937.1	n.1573T>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16528 AN: 151530 Hom.: 937 Cov.: 31

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0694

Gnomad AMR AF: 0.0966

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0856

Gnomad FIN AF: 0.0769

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.0977 AC: 22535 AN: 230736 Hom.: 1314 Cov.: 0 AF XY: 0.0963 AC XY: 11855 AN XY: 123118

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.0901

Gnomad4 ASJ exome AF: 0.140

Gnomad4 EAS exome AF: 0.114

Gnomad4 SAS exome AF: 0.0730

Gnomad4 FIN exome AF: 0.0762

Gnomad4 NFE exome AF: 0.100

Gnomad4 OTH exome AF: 0.102

GnomAD4 genome AF: 0.109 AC: 16573 AN: 151648 Hom.: 952 Cov.: 31 AF XY: 0.108 AC XY: 7994 AN XY: 74086

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.0963

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.0848

Gnomad4 FIN AF: 0.0769

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.122

Alfa AF: 0.101 Hom.: 256

Bravo AF: 0.112

Asia WGS AF: 0.129 AC: 446 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.6
DANN	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs14384; hg19: chr19-2477823;