rs2236518

Positions:

• chr1-3436308-A-C
• chr1-3436308-A-G

Variant summary

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

The NM_022114.4(PRDM16):​c.*2497A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 230,388 control chromosomes in the GnomAD database, including 17,406 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 0.38 (12982 hom., cov: 31)
  • Exomes 𝑓: 0.32 (4424 hom.)
• Consequence: PRDM16 NM_022114.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.49

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM16	NM_022114.4	c.*2497A>C		3_prime_UTR_variant	17/17	ENST00000270722.10	NP_071397.3
PRDM16	NM_199454.3	c.*2497A>C		3_prime_UTR_variant	17/17		NP_955533.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10	c.*2497A>C		3_prime_UTR_variant	17/17	1	NM_022114.4	ENSP00000270722.5

Frequencies

GnomAD3 genomes AF: 0.383 AC: 57889 AN: 151324 Hom.: 12949 Cov.: 31

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.356

GnomAD4 exome AF: 0.316 AC: 24921 AN: 78944 Hom.: 4424 Cov.: 0 AF XY: 0.309 AC XY: 11218 AN XY: 36326

Gnomad4 AFR exome AF: 0.620

Gnomad4 AMR exome AF: 0.370

Gnomad4 ASJ exome AF: 0.243

Gnomad4 EAS exome AF: 0.501

Gnomad4 SAS exome AF: 0.319

Gnomad4 FIN exome AF: 0.243

Gnomad4 NFE exome AF: 0.254

Gnomad4 OTH exome AF: 0.316

GnomAD4 genome AF: 0.383 AC: 57974 AN: 151444 Hom.: 12982 Cov.: 31 AF XY: 0.383 AC XY: 28288 AN XY: 73930

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.358

Alfa AF: 0.282 Hom.: 6269

Bravo AF: 0.402

Asia WGS AF: 0.463 AC: 1610 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.51
DANN	Benign	0.44

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: rs2236518; hg19: chr1-3352872; COSMIC: COSV54585038; COSMIC: COSV54585038;