6-106074152-T-C

Variant names:

• chr6-106074152-T-C
• rs6911490
• ENST00000651185.1:c.-66-14049T>C

Variant summary

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

The ENST00000651185.1(PRDM1):​c.-66-14049T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,262 control chromosomes in the GnomAD database, including 56,349 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 0.86 (56349 hom., cov: 32)
• Consequence: PRDM1 ENST00000651185.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237
• Publications: 26 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM1	XM_017011187.2	c.-66-14049T>C		intron_variant	Intron 1 of 6		XP_016866676.1
PRDM1	XM_047419246.1	c.-66-14049T>C		intron_variant	Intron 2 of 7		XP_047275202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM1	ENST00000651185.1	c.-66-14049T>C		intron_variant	Intron 1 of 6			ENSP00000498716.1
PRDM1	ENST00000652320.1	c.-66-14049T>C		intron_variant	Intron 1 of 6			ENSP00000498580.1
ATG5	ENST00000636437.1	c.458-27327A>G		intron_variant	Intron 6 of 6	5		ENSP00000490376.1
ATG5	ENST00000636335.1	n.*39-1941A>G		intron_variant	Intron 7 of 8	5		ENSP00000490221.1

Frequencies

GnomAD3 genomes AF: 0.856 AC: 130300 AN: 152144 Hom.: 56281 Cov.: 32

Gnomad AFR AF: 0.964

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.861

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.936

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.790

Gnomad OTH AF: 0.836

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

GnomAD4 genome AF: 0.857 AC: 130427 AN: 152262 Hom.: 56349 Cov.: 32 AF XY: 0.858 AC XY: 63889 AN XY: 74436

African (AFR) AF: 0.965 AC: 40075 AN: 41550

American (AMR) AF: 0.861 AC: 13169 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 2766 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5186 AN: 5190

South Asian (SAS) AF: 0.935 AC: 4518 AN: 4830

European-Finnish (FIN) AF: 0.774 AC: 8198 AN: 10592

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.790 AC: 53743 AN: 68022

Other (OTH) AF: 0.838 AC: 1770 AN: 2112

Alfa AF: 0.813 Hom.: 142273

Bravo AF: 0.865

Asia WGS AF: 0.957 AC: 3326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.8
DANN	Benign	0.63
PhyloP100		-0.24

Splicing

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

Other links and lift over

dbSNP: rs6911490; hg19: chr6-106522027;