rs1112213

Variant names:

• chr1-3221135-C-T
• rs1112213
• NM_022114.4:c.388-22952C>T

Variant summary

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

The NM_022114.4(PRDM16):​c.388-22952C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0621 in 152,202 control chromosomes in the GnomAD database, including 641 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 0.062 (641 hom., cov: 33)
• Consequence: PRDM16 NM_022114.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.409
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM16	NM_022114.4	c.388-22952C>T		intron_variant	Intron 2 of 16	ENST00000270722.10	NP_071397.3
PRDM16	NM_199454.3	c.388-22952C>T		intron_variant	Intron 2 of 16		NP_955533.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10	c.388-22952C>T		intron_variant	Intron 2 of 16	1	NM_022114.4	ENSP00000270722.5
PRDM16	ENST00000378391.6	c.388-22952C>T		intron_variant	Intron 2 of 16	1		ENSP00000367643.2
PRDM16	ENST00000511072.5	c.388-22952C>T		intron_variant	Intron 2 of 15	5		ENSP00000426975.1
PRDM16	ENST00000514189.5	c.388-22952C>T		intron_variant	Intron 2 of 15	5		ENSP00000421400.1

Frequencies

GnomAD3 genomes AF: 0.0619 AC: 9409 AN: 152082 Hom.: 633 Cov.: 33

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0366

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0812

Gnomad FIN AF: 0.0610

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00647

Gnomad OTH AF: 0.0450

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

GnomAD4 genome AF: 0.0621 AC: 9450 AN: 152202 Hom.: 641 Cov.: 33 AF XY: 0.0641 AC XY: 4773 AN XY: 74416

African (AFR) AF: 0.161 AC: 6672 AN: 41500

American (AMR) AF: 0.0366 AC: 560 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3468

East Asian (EAS) AF: 0.117 AC: 606 AN: 5168

South Asian (SAS) AF: 0.0813 AC: 392 AN: 4822

European-Finnish (FIN) AF: 0.0610 AC: 647 AN: 10610

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00648 AC: 441 AN: 68012

Other (OTH) AF: 0.0483 AC: 102 AN: 2112

Alfa AF: 0.0500 Hom.: 156

Bravo AF: 0.0645

Asia WGS AF: 0.111 AC: 385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.90
DANN	Benign	0.70
PhyloP100		0.41
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: rs1112213; hg19: chr1-3137699;