rs6924807

Variant names:

• chr6-106083391-G-A
• rs6924807
• ENST00000651185.1:c.-66-4810G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-106083391-G-A
• chr6-106083391-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000651185.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM1	ENST00000651185.1		c.-66-4810G>A		intron	N/A	ENSP00000498716.1
	PRDM1	ENST00000652320.1		c.-66-4810G>A		intron	N/A	ENSP00000498580.1
	ATG5	ENST00000636437.1	TSL:5	c.458-36566C>T		intron	N/A	ENSP00000490376.1

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

African (AFR) AF: 0.839 AC: 34757 AN: 41414

American (AMR) AF: 0.488 AC: 7431 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2287 AN: 3464

East Asian (EAS) AF: 0.564 AC: 2917 AN: 5174

South Asian (SAS) AF: 0.476 AC: 2286 AN: 4804

European-Finnish (FIN) AF: 0.489 AC: 5129 AN: 10494

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.604 AC: 41018 AN: 67898

Other (OTH) AF: 0.653 AC: 1377 AN: 2108

Alfa AF: 0.598 Hom.: 6795

Bravo AF: 0.656

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.50
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs6924807; hg19: chr6-106531266;