rs2500247

Variant names:

• chr1-3265843-G-C
• rs2500247
• NM_022114.4:c.438+21706G>C

Variant summary

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

The NM_022114.4(PRDM16):​c.438+21706G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,034 control chromosomes in the GnomAD database, including 4,778 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 0.22 (4778 hom., cov: 32)
• Consequence: PRDM16 NM_022114.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105
• Publications: 3 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):

• left ventricular noncompaction 8

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

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.362 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.438+21706G>C		intron	N/A	NP_071397.3
	PRDM16	NM_199454.3		c.438+21706G>C		intron	N/A	NP_955533.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM16	ENST00000270722.10	TSL:1 MANE Select	c.438+21706G>C		intron	N/A	ENSP00000270722.5
	PRDM16	ENST00000378391.6	TSL:1	c.438+21706G>C		intron	N/A	ENSP00000367643.2
	PRDM16	ENST00000512462.5	TSL:1	n.216+21706G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33963 AN: 151916 Hom.: 4757 Cov.: 32

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.224 AC: 34028 AN: 152034 Hom.: 4778 Cov.: 32 AF XY: 0.224 AC XY: 16619 AN XY: 74310

African (AFR) AF: 0.366 AC: 15180 AN: 41422

American (AMR) AF: 0.322 AC: 4922 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 733 AN: 3472

East Asian (EAS) AF: 0.192 AC: 992 AN: 5156

South Asian (SAS) AF: 0.210 AC: 1011 AN: 4816

European-Finnish (FIN) AF: 0.103 AC: 1091 AN: 10610

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9484 AN: 67964

Other (OTH) AF: 0.226 AC: 477 AN: 2110

Alfa AF: 0.183 Hom.: 413

Bravo AF: 0.247

Asia WGS AF: 0.192 AC: 667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.1
DANN	Benign	0.38
PhyloP100		-0.10
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: rs2500247; hg19: chr1-3182407;