rs3117582

Positions:

• chr6-31652743-T-G

Variant summary

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

The ENST00000375920.8(APOM):​c.-103+192T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0693 in 153,158 control chromosomes in the GnomAD database, including 513 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 0.069 (508 hom., cov: 32)
  • Exomes 𝑓: 0.054 (5 hom.)
• Consequence: APOM ENST00000375920.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270

Genes affected

APOM (HGNC:13916): (apolipoprotein M) The protein encoded by this gene is an apolipoprotein and member of the lipocalin protein family. It is found associated with high density lipoproteins and to a lesser extent with low density lipoproteins and triglyceride-rich lipoproteins. The encoded protein is secreted through the plasma membrane but remains membrane-bound, where it is involved in lipid transport. Alternate splicing results in both coding and non-coding variants of this gene. [provided by RefSeq, Jan 2012]

BAG6 (HGNC:13919): (BAG cochaperone 6) This gene was first characterized as part of a cluster of genes located within the human major histocompatibility complex class III region. This gene encodes a nuclear protein that is cleaved by caspase 3 and is implicated in the control of apoptosis. In addition, the protein forms a complex with E1A binding protein p300 and is required for the acetylation of p53 in response to DNA damage. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOM	NM_001256169.2	c.-103+192T>G		intron_variant
APOM	NR_045828.2	n.148+192T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOM	ENST00000375920.8	c.-103+192T>G		intron_variant		1
APOM	ENST00000375918.6	c.-103+192T>G		intron_variant		2
BAG6	ENST00000211379.9			upstream_gene_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.0694 AC: 10559 AN: 152098 Hom.: 508 Cov.: 32

Gnomad AFR AF: 0.0388

Gnomad AMI AF: 0.0692

Gnomad AMR AF: 0.0316

Gnomad ASJ AF: 0.0397

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0784

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0516

GnomAD4 exome AF: 0.0541 AC: 51 AN: 942 Hom.: 5 Cov.: 0 AF XY: 0.0529 AC XY: 31 AN XY: 586

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0893

Gnomad4 NFE exome AF: 0.0712

Gnomad4 OTH exome AF: 0.0641

GnomAD4 genome AF: 0.0694 AC: 10558 AN: 152216 Hom.: 508 Cov.: 32 AF XY: 0.0647 AC XY: 4818 AN XY: 74424

Gnomad4 AFR AF: 0.0387

Gnomad4 AMR AF: 0.0315

Gnomad4 ASJ AF: 0.0397

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0784

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0964 Hom.: 1453

Bravo AF: 0.0650

Asia WGS AF: 0.00693 AC: 25 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.9
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3117582; hg19: chr6-31620520; COSMIC: COSV52990728; COSMIC: COSV52990728;