rs3783501

Positions:

• chr19-2477318-G-A

Variant summary

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

The ENST00000215631.9(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 ENST00000215631.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474

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 (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/exons	MANE	Protein	UniProt
GADD45B	NM_015675.4	c.369+67G>A		intron_variant		ENST00000215631.9	NP_056490.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GADD45B	ENST00000215631.9	c.369+67G>A		intron_variant		1	NM_015675.4	ENSP00000215631	P1
GADD45B	ENST00000587345.1	c.436G>A	p.Gly146Arg	missense_variant	3/3	2		ENSP00000467490
GADD45B	ENST00000592937.1	n.1066G>A		non_coding_transcript_exon_variant	2/2	2
GADD45B	ENST00000585359.1	c.*184+67G>A		intron_variant, NMD_transcript_variant		3		ENSP00000466414

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

GnomAD3 exomes AF: 0.518 AC: 54918 AN: 105922 Hom.: 14413 AF XY: 0.525 AC XY: 29045 AN XY: 55288

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 SAS exome AF: 0.572

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

Gnomad4 AFR exome AF: 0.309

Gnomad4 AMR exome AF: 0.552

Gnomad4 ASJ exome AF: 0.563

Gnomad4 EAS exome AF: 0.462

Gnomad4 SAS exome AF: 0.564

Gnomad4 FIN exome AF: 0.418

Gnomad4 NFE exome AF: 0.532

Gnomad4 OTH exome AF: 0.532

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

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.449

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.543

Alfa AF: 0.532 Hom.: 27703

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
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
MutationTaster	Benign	1.0	P;P
Vest4		0.11
GERP RS		-9.1

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: rs3783501; hg19: chr19-2477316; COSMIC: COSV53126456; COSMIC: COSV53126456;