rs3783501

Variant names:

• chr19-2477318-G-A
• rs3783501
• NM_015675.4:c.369+67G>A

Variant summary

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

The NM_015675.4(GADD45B):​c.369+67G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 1,203,168 control chromosomes in the GnomAD database, including 163,310 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 0.47 (17471 hom., cov: 32)
  • Exomes 𝑓: 0.52 (145839 hom.)
• Consequence: GADD45B NM_015675.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474
• Publications: 23 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 (MetaRNN=3.5640966E-5).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GADD45B	NM_015675.4	c.369+67G>A		intron_variant	Intron 3 of 3	ENST00000215631.9	NP_056490.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GADD45B	ENST00000215631.9	c.369+67G>A		intron_variant	Intron 3 of 3	1	NM_015675.4	ENSP00000215631.3

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70902 AN: 151942 Hom.: 17445 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.538

GnomAD2 exomes AF: 0.518 AC: 54918 AN: 105922 AF XY: 0.525

Gnomad AFR exome AF: 0.316

Gnomad AMR exome AF: 0.555

Gnomad ASJ exome AF: 0.561

Gnomad EAS exome AF: 0.438

Gnomad FIN exome AF: 0.428

Gnomad NFE exome AF: 0.544

Gnomad OTH exome AF: 0.559

GnomAD4 exome AF: 0.524 AC: 551013 AN: 1051108 Hom.: 145839 Cov.: 14 AF XY: 0.526 AC XY: 275795 AN XY: 524612

African (AFR) AF: 0.309 AC: 7649 AN: 24762

American (AMR) AF: 0.552 AC: 15435 AN: 27946

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 10586 AN: 18816

East Asian (EAS) AF: 0.462 AC: 15913 AN: 34442

South Asian (SAS) AF: 0.564 AC: 36908 AN: 65400

European-Finnish (FIN) AF: 0.418 AC: 14286 AN: 34212

Middle Eastern (MID) AF: 0.624 AC: 2521 AN: 4038

European-Non Finnish (NFE) AF: 0.532 AC: 423045 AN: 795138

Other (OTH) AF: 0.532 AC: 24670 AN: 46354

GnomAD4 genome AF: 0.467 AC: 70968 AN: 152060 Hom.: 17471 Cov.: 32 AF XY: 0.463 AC XY: 34445 AN XY: 74328

African (AFR) AF: 0.326 AC: 13497 AN: 41464

American (AMR) AF: 0.573 AC: 8756 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1934 AN: 3468

East Asian (EAS) AF: 0.449 AC: 2321 AN: 5174

South Asian (SAS) AF: 0.567 AC: 2735 AN: 4820

European-Finnish (FIN) AF: 0.396 AC: 4188 AN: 10580

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35747 AN: 67944

Other (OTH) AF: 0.543 AC: 1148 AN: 2114

Alfa AF: 0.523 Hom.: 40962

Bravo AF: 0.473

TwinsUK AF: 0.527 AC: 1954

ALSPAC AF: 0.532 AC: 2049

ExAC AF: 0.421 AC: 43905

Asia WGS AF: 0.550 AC: 1915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	4.8
DANN	Benign	0.89
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.39	T
MetaRNN	Benign	0.000036	T
PhyloP100		-0.47
Vest4		0.11
GERP RS		-9.1
Mutation Taster		=99/1	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: rs3783501; hg19: chr19-2477316; COSMIC: COSV53126456; COSMIC: COSV53126456;