rs707921

Positions:

• chr6-31657764-C-A

Variant summary

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

The NM_019101.3(APOM):​c.541+41C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0452 in 1,538,572 control chromosomes in the GnomAD database, including 3,093 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 0.086 (956 hom., cov: 32)
  • Exomes 𝑓: 0.041 (2137 hom.)
• Consequence: APOM NM_019101.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOM	NM_019101.3	c.541+41C>A		intron_variant		ENST00000375916.4	NP_061974.2
APOM	NM_001256169.2	c.325+41C>A		intron_variant			NP_001243098.1
APOM	XM_006715150.4	c.445+41C>A		intron_variant			XP_006715213.1
APOM	NR_045828.2	n.582+41C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOM	ENST00000375916.4	c.541+41C>A		intron_variant		1	NM_019101.3	ENSP00000365081	P1
APOM	ENST00000375920.8	c.325+41C>A		intron_variant		1		ENSP00000365085
APOM	ENST00000375918.6	c.366C>A	p.Thr122=	synonymous_variant	5/5	2		ENSP00000365083

Frequencies

GnomAD3 genomes AF: 0.0862 AC: 13103 AN: 152022 Hom.: 956 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0765

Gnomad ASJ AF: 0.0507

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.0626

Gnomad FIN AF: 0.00481

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0312

Gnomad OTH AF: 0.0955

GnomAD3 exomes AF: 0.0570 AC: 14126 AN: 247858 Hom.: 813 AF XY: 0.0540 AC XY: 7265 AN XY: 134586

Gnomad AFR exome AF: 0.203

Gnomad AMR exome AF: 0.0702

Gnomad ASJ exome AF: 0.0495

Gnomad EAS exome AF: 0.146

Gnomad SAS exome AF: 0.0556

Gnomad FIN exome AF: 0.00366

Gnomad NFE exome AF: 0.0295

Gnomad OTH exome AF: 0.0537

GnomAD4 exome AF: 0.0407 AC: 56476 AN: 1386432 Hom.: 2137 Cov.: 23 AF XY: 0.0406 AC XY: 28167 AN XY: 694048

Gnomad4 AFR exome AF: 0.208

Gnomad4 AMR exome AF: 0.0725

Gnomad4 ASJ exome AF: 0.0519

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.0553

Gnomad4 FIN exome AF: 0.00521

Gnomad4 NFE exome AF: 0.0307

Gnomad4 OTH exome AF: 0.0579

GnomAD4 genome AF: 0.0862 AC: 13110 AN: 152140 Hom.: 956 Cov.: 32 AF XY: 0.0859 AC XY: 6387 AN XY: 74384

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.0764

Gnomad4 ASJ AF: 0.0507

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.0624

Gnomad4 FIN AF: 0.00481

Gnomad4 NFE AF: 0.0312

Gnomad4 OTH AF: 0.0964

Alfa AF: 0.0491 Hom.: 625

Bravo AF: 0.0967

Asia WGS AF: 0.0920 AC: 318 AN: 3478

EpiCase AF: 0.0358

EpiControl AF: 0.0364

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs707921; hg19: chr6-31625541; COSMIC: COSV65524048; COSMIC: COSV65524048;