rs805264

Positions:

• chr6-31656096-G-A

Variant summary

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

The ENST00000375916.4(APOM):​c.114+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0399 in 1,547,002 control chromosomes in the GnomAD database, including 2,040 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 0.066 (507 hom., cov: 32)
  • Exomes 𝑓: 0.037 (1533 hom.)
• Consequence: APOM ENST00000375916.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOM	NM_019101.3	c.114+16G>A		intron_variant		ENST00000375916.4	NP_061974.2
APOM	NM_001256169.2	c.-102-376G>A		intron_variant			NP_001243098.1
APOM	XM_006715150.4	c.11+16G>A		intron_variant			XP_006715213.1
APOM	NR_045828.2	n.149-376G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOM	ENST00000375916.4	c.114+16G>A		intron_variant		1	NM_019101.3	ENSP00000365081	P1
APOM	ENST00000375920.8	c.-102-376G>A		intron_variant		1		ENSP00000365085
APOM	ENST00000375918.6	c.-102-376G>A		intron_variant		2		ENSP00000365083

Frequencies

GnomAD3 genomes AF: 0.0660 AC: 10048 AN: 152140 Hom.: 507 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0615

Gnomad ASJ AF: 0.0502

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.0599

Gnomad FIN AF: 0.00584

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0289

Gnomad OTH AF: 0.0728

GnomAD3 exomes AF: 0.0508 AC: 8002 AN: 157474 Hom.: 385 AF XY: 0.0501 AC XY: 4205 AN XY: 83886

Gnomad AFR exome AF: 0.144

Gnomad AMR exome AF: 0.0531

Gnomad ASJ exome AF: 0.0498

Gnomad EAS exome AF: 0.144

Gnomad SAS exome AF: 0.0551

Gnomad FIN exome AF: 0.00448

Gnomad NFE exome AF: 0.0293

Gnomad OTH exome AF: 0.0543

GnomAD4 exome AF: 0.0371 AC: 51742 AN: 1394744 Hom.: 1533 Cov.: 28 AF XY: 0.0372 AC XY: 25633 AN XY: 688832

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.0550

Gnomad4 ASJ exome AF: 0.0516

Gnomad4 EAS exome AF: 0.0932

Gnomad4 SAS exome AF: 0.0542

Gnomad4 FIN exome AF: 0.00615

Gnomad4 NFE exome AF: 0.0300

Gnomad4 OTH exome AF: 0.0521

GnomAD4 genome AF: 0.0660 AC: 10052 AN: 152258 Hom.: 507 Cov.: 32 AF XY: 0.0660 AC XY: 4916 AN XY: 74442

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.0614

Gnomad4 ASJ AF: 0.0502

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.0598

Gnomad4 FIN AF: 0.00584

Gnomad4 NFE AF: 0.0289

Gnomad4 OTH AF: 0.0725

Alfa AF: 0.0407 Hom.: 332

Bravo AF: 0.0736

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs805264; hg19: chr6-31623873; COSMIC: COSV52990956; COSMIC: COSV52990956;