chr19-2477825-T-C

Variant names:

• chr19-2477825-T-C
• rs14384
• NM_015675.4:c.*224T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GADD45B	NM_015675.4	c.*224T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000215631.9	NP_056490.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GADD45B	ENST00000215631.9	c.*224T>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_015675.4	ENSP00000215631.3
GADD45B	ENST00000592937.1	n.1573T>C		non_coding_transcript_exon_variant	Exon 2 of 2	2
GADD45B	ENST00000718317.1	c.*196T>C		3_prime_UTR_variant	Exon 3 of 3			ENSP00000520751.1
GADD45B	ENST00000585359.1	n.*522T>C		downstream_gene_variant		3		ENSP00000466414.1

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

African (AFR) AF: 0.126 AC: 882 AN: 6982

American (AMR) AF: 0.0901 AC: 962 AN: 10678

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 980 AN: 7018

East Asian (EAS) AF: 0.114 AC: 1374 AN: 12064

South Asian (SAS) AF: 0.0730 AC: 2471 AN: 33828

European-Finnish (FIN) AF: 0.0762 AC: 853 AN: 11198

Middle Eastern (MID) AF: 0.148 AC: 142 AN: 962

European-Non Finnish (NFE) AF: 0.100 AC: 13560 AN: 135090

Other (OTH) AF: 0.102 AC: 1311 AN: 12916

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

African (AFR) AF: 0.130 AC: 5384 AN: 41352

American (AMR) AF: 0.0963 AC: 1470 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 493 AN: 3464

East Asian (EAS) AF: 0.118 AC: 600 AN: 5106

South Asian (SAS) AF: 0.0848 AC: 406 AN: 4786

European-Finnish (FIN) AF: 0.0769 AC: 807 AN: 10498

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7037 AN: 67886

Other (OTH) AF: 0.122 AC: 256 AN: 2094

Alfa AF: 0.103 Hom.: 333

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
PhyloP100		0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs14384; hg19: chr19-2477823;