1-3069321-C-G

Position:

• chr1-3069321-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022114.4(PRDM16):​c.37+25C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,264,322 control chromosomes in the GnomAD database, including 101,620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (10340 hom., cov: 27)
  • Exomes 𝑓: 0.40 (91280 hom.)
• Consequence: PRDM16 NM_022114.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.240

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]

LOC124903827 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 1-3069321-C-G is Benign according to our data. Variant chr1-3069321-C-G is described in ClinVar as [Benign]. Clinvar id is 674706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM16	NM_022114.4	c.37+25C>G		intron_variant		ENST00000270722.10	NP_071397.3
LOC124903827	XM_047436614.1	c.1651-350G>C		intron_variant			XP_047292570.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10	c.37+25C>G		intron_variant		1	NM_022114.4	ENSP00000270722	P1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 50703 AN: 142982 Hom.: 10344 Cov.: 27

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.354

GnomAD3 exomes AF: 0.459 AC: 62080 AN: 135242 Hom.: 14484 AF XY: 0.451 AC XY: 34427 AN XY: 76276

Gnomad AFR exome AF: 0.172

Gnomad AMR exome AF: 0.611

Gnomad ASJ exome AF: 0.434

Gnomad EAS exome AF: 0.585

Gnomad SAS exome AF: 0.405

Gnomad FIN exome AF: 0.538

Gnomad NFE exome AF: 0.420

Gnomad OTH exome AF: 0.409

GnomAD4 exome AF: 0.397 AC: 445017 AN: 1121338 Hom.: 91280 Cov.: 25 AF XY: 0.397 AC XY: 218309 AN XY: 549500

Gnomad4 AFR exome AF: 0.139

Gnomad4 AMR exome AF: 0.587

Gnomad4 ASJ exome AF: 0.416

Gnomad4 EAS exome AF: 0.579

Gnomad4 SAS exome AF: 0.394

Gnomad4 FIN exome AF: 0.521

Gnomad4 NFE exome AF: 0.391

Gnomad4 OTH exome AF: 0.390

GnomAD4 genome AF: 0.354 AC: 50681 AN: 142984 Hom.: 10340 Cov.: 27 AF XY: 0.365 AC XY: 25374 AN XY: 69436

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.559

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.354

Alfa AF: 0.247 Hom.: 731

Bravo AF: 0.348

Asia WGS AF: 0.375 AC: 1142 AN: 3050

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 15, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	16
DANN	Benign	0.66

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: rs7413494; hg19: chr1-2985885;