rs2483280

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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]

PRDM16 Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AD Classification: STRONG Submitted by: ClinGen
• left ventricular noncompaction 8

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• left ventricular noncompaction

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022114.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM16	NM_022114.4	MANE Select	c.439-46177G>A		intron	N/A	NP_071397.3
	PRDM16	NM_199454.3		c.439-46177G>A		intron	N/A	NP_955533.2	Q9HAZ2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM16	ENST00000270722.10	TSL:1 MANE Select	c.439-46177G>A		intron	N/A	ENSP00000270722.5	Q9HAZ2-1
	PRDM16	ENST00000378391.6	TSL:1	c.439-46177G>A		intron	N/A	ENSP00000367643.2	Q9HAZ2-2
	PRDM16	ENST00000512462.5	TSL:1	n.217-46177G>A		intron	N/A

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

African (AFR) AF: 0.121 AC: 5043 AN: 41508

American (AMR) AF: 0.245 AC: 3747 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1468 AN: 3458

East Asian (EAS) AF: 0.196 AC: 1009 AN: 5140

South Asian (SAS) AF: 0.440 AC: 2123 AN: 4820

European-Finnish (FIN) AF: 0.363 AC: 3842 AN: 10584

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26776 AN: 67952

Other (OTH) AF: 0.318 AC: 672 AN: 2110

Alfa AF: 0.356 Hom.: 16697

Bravo AF: 0.275

Asia WGS AF: 0.260 AC: 905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.13
DANN	Benign	0.38
PhyloP100		-5.3
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: rs2483280; hg19: chr1-3255539;