rs2483280

Variant names:

• chr1-3338975-G-A
• rs2483280
• NM_022114.4:c.439-46177G>A

Variant summary

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

The NM_022114.4(PRDM16):​c.439-46177G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,060 control chromosomes in the GnomAD database, including 7,938 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 0.30 (7938 hom., cov: 32)
• Consequence: PRDM16 NM_022114.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.34

Genes affected

PRDM16 (HGNC:14000): (PR/SET domain 16) The reciprocal translocation t(1;3)(p36;q21) occurs in a subset of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). This gene is located near the 1p36.3 breakpoint and has been shown to be specifically expressed in the t(1:3)(p36,q21)-positive MDS/AML. The protein encoded by this gene is a zinc finger transcription factor and contains an N-terminal PR domain. The translocation results in the overexpression of a truncated version of this protein that lacks the PR domain, which may play an important role in the pathogenesis of MDS and AML. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM16	NM_022114.4	c.439-46177G>A		intron_variant	Intron 3 of 16	ENST00000270722.10	NP_071397.3
PRDM16	NM_199454.3	c.439-46177G>A		intron_variant	Intron 3 of 16		NP_955533.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10	c.439-46177G>A		intron_variant	Intron 3 of 16	1	NM_022114.4	ENSP00000270722.5

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45235 AN: 151942 Hom.: 7941 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.323

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.297 AC: 45237 AN: 152060 Hom.: 7938 Cov.: 32 AF XY: 0.297 AC XY: 22044 AN XY: 74334

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.318

Alfa AF: 0.325 Hom.: 1848

Bravo AF: 0.275

Asia WGS AF: 0.260 AC: 905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.13
DANN	Benign	0.38

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: rs2483280; hg19: chr1-3255539;