rs2500295

Positions:

• chr1-3292932-T-C
• chr1-3292932-T-G

Variant summary

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

The NM_022114.4(PRDM16):​c.438+48795T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,188 control chromosomes in the GnomAD database, including 48,869 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 0.80 (48869 hom., cov: 33)
• Consequence: PRDM16 NM_022114.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.849

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM16	NM_022114.4	c.438+48795T>C		intron_variant		ENST00000270722.10	NP_071397.3
LOC124903828	XM_047436627.1	c.*4950T>C		3_prime_UTR_variant	1/2		XP_047292583.1
PRDM16	NM_199454.3	c.438+48795T>C		intron_variant			NP_955533.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10	c.438+48795T>C		intron_variant		1	NM_022114.4	ENSP00000270722.5

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121562 AN: 152070 Hom.: 48804 Cov.: 33

Gnomad AFR AF: 0.822

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.785

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

GnomAD4 genome AF: 0.800 AC: 121690 AN: 152188 Hom.: 48869 Cov.: 33 AF XY: 0.800 AC XY: 59563 AN XY: 74408

Gnomad4 AFR AF: 0.822

Gnomad4 AMR AF: 0.829

Gnomad4 ASJ AF: 0.713

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.816

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.788

Alfa AF: 0.727 Hom.: 2422

Bravo AF: 0.805

Asia WGS AF: 0.876 AC: 3044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.6
DANN	Benign	0.46

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: rs2500295; hg19: chr1-3209496;