chr1-67685248-T-G

Position:

• chr1-67685248-T-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001924.4(GADD45A):​c.-247T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000701 in 501,814 control chromosomes in the GnomAD database, including 3 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 0.0017 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00025 (0 hom.)
• Consequence: GADD45A NM_001924.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48

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

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BS2: High AC in GnomAd4 at 264 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GADD45A	NM_001924.4	c.-247T>G		5_prime_UTR_variant	1/4	ENST00000370986.9
GADD45A	NM_001199741.2	c.-247T>G		5_prime_UTR_variant	1/3
GADD45A	NM_001199742.2	c.-247T>G		5_prime_UTR_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GADD45A	ENST00000370986.9	c.-247T>G		5_prime_UTR_variant	1/4	1	NM_001924.4	P1

Frequencies

GnomAD3 genomes AF: 0.00174 AC: 264 AN: 152084 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00609

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.000252 AC: 88 AN: 349618 Hom.: 0 Cov.: 0 AF XY: 0.000182 AC XY: 34 AN XY: 186586

Gnomad4 AFR exome AF: 0.00767

Gnomad4 AMR exome AF: 0.000618

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000294

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000686

Gnomad4 OTH exome AF: 0.000623

GnomAD4 genome AF: 0.00173 AC: 264 AN: 152196 Hom.: 3 Cov.: 33 AF XY: 0.00177 AC XY: 132 AN XY: 74406

Gnomad4 AFR AF: 0.00609

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00205 Hom.: 0

Bravo AF: 0.00219

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.7
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs3783460; hg19: chr1-68150931;