NM_001198.4:c.291+1426G>A

Variant names:

• chr6-106089875-G-A
• rs6923419
• NM_001198.4:c.291+1426G>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.291+1426G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,102 control chromosomes in the GnomAD database, including 3,521 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 0.19 (3521 hom., cov: 32)
• Consequence: PRDM1 NM_001198.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122
• Publications: 6 publications found

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]

ATG5 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia, autosomal recessive 25

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM1	NM_001198.4	MANE Select	c.291+1426G>A		intron	N/A	NP_001189.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM1	ENST00000369096.9	TSL:1 MANE Select	c.291+1426G>A		intron	N/A	ENSP00000358092.4
	PRDM1	ENST00000369091.6	TSL:1	c.183+1426G>A		intron	N/A	ENSP00000358087.2
	PRDM1	ENST00000648754.1		c.333+1426G>A		intron	N/A	ENSP00000498029.1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28123 AN: 151984 Hom.: 3517 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0785

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.0775

Gnomad FIN AF: 0.0670

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.185 AC: 28155 AN: 152102 Hom.: 3521 Cov.: 32 AF XY: 0.178 AC XY: 13257 AN XY: 74368

African (AFR) AF: 0.353 AC: 14635 AN: 41424

American (AMR) AF: 0.118 AC: 1797 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0785 AC: 272 AN: 3466

East Asian (EAS) AF: 0.210 AC: 1090 AN: 5188

South Asian (SAS) AF: 0.0771 AC: 372 AN: 4824

European-Finnish (FIN) AF: 0.0670 AC: 709 AN: 10584

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8780 AN: 68010

Other (OTH) AF: 0.158 AC: 333 AN: 2114

Alfa AF: 0.139 Hom.: 4742

Bravo AF: 0.199

Asia WGS AF: 0.124 AC: 434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.74
PhyloP100		-0.12
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: rs6923419; hg19: chr6-106537750; COSMIC: COSV64848685;