chr6-106083391-G-A

Position:

• chr6-106083391-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000651185.1(PRDM1):​c.-66-4810G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 151,788 control chromosomes in the GnomAD database, including 33,039 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 0.65 (33039 hom., cov: 29)
• Consequence: PRDM1 ENST00000651185.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM1	XM_017011187.2	c.-66-4810G>A		intron_variant			XP_016866676.1
PRDM1	XM_047419246.1	c.-66-4810G>A		intron_variant			XP_047275202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM1	ENST00000651185.1	c.-66-4810G>A		intron_variant				ENSP00000498716.1
PRDM1	ENST00000652320.1	c.-66-4810G>A		intron_variant				ENSP00000498580.1
ATG5	ENST00000636437.1	c.458-36566C>T		intron_variant		5		ENSP00000490376.1
ATG5	ENST00000636335.1	n.458-5076C>T		intron_variant		5		ENSP00000490221.1

Frequencies

GnomAD3 genomes AF: 0.645 AC: 97879 AN: 151672 Hom.: 32982 Cov.: 29

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.646 AC: 97988 AN: 151788 Hom.: 33039 Cov.: 29 AF XY: 0.634 AC XY: 47020 AN XY: 74144

Gnomad4 AFR AF: 0.839

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.489

Gnomad4 NFE AF: 0.604

Gnomad4 OTH AF: 0.653

Alfa AF: 0.584 Hom.: 5671

Bravo AF: 0.656

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.50

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6924807; hg19: chr6-106531266;