1-3069321-C-G

Variant names:

• chr1-3069321-C-G
• rs7413494
• NM_022114.4:c.37+25C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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-DT (HGNC:48664): (PRDM16 divergent transcript)

LOC124903827 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PRDM16	NM_022114.4	c.37+25C>G		intron_variant	Intron 1 of 16	ENST00000270722.10	NP_071397.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10	c.37+25C>G		intron_variant	Intron 1 of 16	1	NM_022114.4	ENSP00000270722.5

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

GnomAD2 exomes AF: 0.459 AC: 62080 AN: 135242 AF XY: 0.451

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 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

African (AFR) AF: 0.139 AC: 3236 AN: 23218

American (AMR) AF: 0.587 AC: 13964 AN: 23778

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 6670 AN: 16048

East Asian (EAS) AF: 0.579 AC: 10926 AN: 18858

South Asian (SAS) AF: 0.394 AC: 20748 AN: 52726

European-Finnish (FIN) AF: 0.521 AC: 15461 AN: 29692

Middle Eastern (MID) AF: 0.338 AC: 1026 AN: 3036

European-Non Finnish (NFE) AF: 0.391 AC: 357056 AN: 913110

Other (OTH) AF: 0.390 AC: 15930 AN: 40872

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

African (AFR) AF: 0.160 AC: 6408 AN: 40030

American (AMR) AF: 0.499 AC: 7309 AN: 14636

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1409 AN: 3360

East Asian (EAS) AF: 0.559 AC: 2576 AN: 4608

South Asian (SAS) AF: 0.410 AC: 1921 AN: 4690

European-Finnish (FIN) AF: 0.551 AC: 4397 AN: 7976

Middle Eastern (MID) AF: 0.279 AC: 77 AN: 276

European-Non Finnish (NFE) AF: 0.397 AC: 25613 AN: 64544

Other (OTH) AF: 0.354 AC: 702 AN: 1982

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		0.24
PromoterAI		-0.013	Neutral
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: rs7413494; hg19: chr1-2985885;