rs2185379

Variant names:

• chr6-106088378-G-A
• rs2185379
• NM_001198.4:c.220G>A

Variant summary

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

The NM_001198.4(PRDM1):​c.220G>A​(p.Gly74Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 1,614,036 control chromosomes in the GnomAD database, including 1,396 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.045 (209 hom., cov: 32)
  • Exomes 𝑓: 0.036 (1187 hom.)
• Consequence: PRDM1 NM_001198.4 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 2.75

Genes affected

PRDM1 (HGNC:9346): (PR/SET domain 1) This gene encodes a protein that acts as a repressor of beta-interferon gene expression. The protein binds specifically to the PRDI (positive regulatory domain I element) of the beta-IFN gene promoter. Transcription of this gene increases upon virus induction. Two alternatively spliced transcript variants that encode different isoforms have been reported. [provided by RefSeq, Jul 2008]

ATG5 (HGNC:589): (autophagy related 5) The protein encoded by this gene, in combination with autophagy protein 12, functions as an E1-like activating enzyme in a ubiquitin-like conjugating system. The encoded protein is involved in several cellular processes, including autophagic vesicle formation, mitochondrial quality control after oxidative damage, negative regulation of the innate antiviral immune response, lymphocyte development and proliferation, MHC II antigen presentation, adipocyte differentiation, and apoptosis. Several transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017325878).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM1	NM_001198.4	c.220G>A	p.Gly74Ser	missense_variant	Exon 2 of 7	ENST00000369096.9	NP_001189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM1	ENST00000369096.9	c.220G>A	p.Gly74Ser	missense_variant	Exon 2 of 7	1	NM_001198.4	ENSP00000358092.4

Frequencies

GnomAD3 genomes AF: 0.0452 AC: 6869 AN: 152050 Hom.: 206 Cov.: 32

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0361

Gnomad ASJ AF: 0.0397

Gnomad EAS AF: 0.0715

Gnomad SAS AF: 0.0572

Gnomad FIN AF: 0.0227

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0315

Gnomad OTH AF: 0.0398

GnomAD2 exomes AF: 0.0377 AC: 9491 AN: 251492 AF XY: 0.0385

Gnomad AFR exome AF: 0.0690

Gnomad AMR exome AF: 0.0193

Gnomad ASJ exome AF: 0.0368

Gnomad EAS exome AF: 0.0590

Gnomad FIN exome AF: 0.0235

Gnomad NFE exome AF: 0.0318

Gnomad OTH exome AF: 0.0384

GnomAD4 exome AF: 0.0356 AC: 52021 AN: 1461868 Hom.: 1187 Cov.: 32 AF XY: 0.0365 AC XY: 26562 AN XY: 727240

Gnomad4 AFR exome AF: 0.0742 AC: 2485 AN: 33478

Gnomad4 AMR exome AF: 0.0220 AC: 983 AN: 44724

Gnomad4 ASJ exome AF: 0.0363 AC: 950 AN: 26136

Gnomad4 EAS exome AF: 0.0990 AC: 3929 AN: 39700

Gnomad4 SAS exome AF: 0.0617 AC: 5320 AN: 86258

Gnomad4 FIN exome AF: 0.0218 AC: 1165 AN: 53420

Gnomad4 NFE exome AF: 0.0310 AC: 34425 AN: 1111992

Gnomad4 Remaining exome AF: 0.0410 AC: 2475 AN: 60392

GnomAD4 genome AF: 0.0452 AC: 6885 AN: 152168 Hom.: 209 Cov.: 32 AF XY: 0.0449 AC XY: 3340 AN XY: 74396

Gnomad4 AFR AF: 0.0716 AC: 0.0716352 AN: 0.0716352

Gnomad4 AMR AF: 0.0360 AC: 0.0360366 AN: 0.0360366

Gnomad4 ASJ AF: 0.0397 AC: 0.0397465 AN: 0.0397465

Gnomad4 EAS AF: 0.0718 AC: 0.0718147 AN: 0.0718147

Gnomad4 SAS AF: 0.0570 AC: 0.0570066 AN: 0.0570066

Gnomad4 FIN AF: 0.0227 AC: 0.0227316 AN: 0.0227316

Gnomad4 NFE AF: 0.0315 AC: 0.0314954 AN: 0.0314954

Gnomad4 OTH AF: 0.0455 AC: 0.0454976 AN: 0.0454976

Alfa AF: 0.0376 Hom.: 589

Bravo AF: 0.0464

TwinsUK AF: 0.0289 AC: 107

ALSPAC AF: 0.0311 AC: 120

ESP6500AA AF: 0.0704 AC: 310

ESP6500EA AF: 0.0323 AC: 278

ExAC AF: 0.0396 AC: 4802

Asia WGS AF: 0.100 AC: 347 AN: 3478

EpiCase AF: 0.0310

EpiControl AF: 0.0334

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

Sep 19, 2013

ITMI

Significance: not provided

Review Status: no classification provided

Collection Method: reference population

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	20
DANN	Benign	0.63
DEOGEN2	Benign	0.23	.;T;.;.
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.81	T;T;T;T
MetaRNN	Benign	0.0017	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	.;L;.;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.040	N;N;N;.
REVEL	Benign	0.054
Sift	Benign	0.59	T;T;T;.
Sift4G	Benign	1.0	T;T;T;.
Polyphen		0.016	.;B;.;.
Vest4		0.035
MPC		0.38
ClinPred		0.016	T
GERP RS		4.0
Varity_R		0.052
gMVP		0.60
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

Publications

LitVar

Other links and lift over

dbSNP: rs2185379; hg19: chr6-106536253; COSMIC: COSV64850169;