6-31657730-G-T

Variant names:

• chr6-31657730-G-T
• rs707922
• NM_019101.3:c.541+7G>T

Variant summary

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

The NM_019101.3(APOM):​c.541+7G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0739 in 1,606,622 control chromosomes in the GnomAD database, including 8,216 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (2549 hom., cov: 32)
  • Exomes 𝑓: 0.067 (5667 hom.)
• Consequence: APOM NM_019101.3 splice_region, intron
• Scores: Splicing: ADA: 0.00001998
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.862
• Publications: 26 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0012431145).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOM	NM_019101.3	c.541+7G>T		splice_region_variant, intron_variant	Intron 5 of 5	ENST00000375916.4	NP_061974.2
APOM	NM_001256169.2	c.325+7G>T		splice_region_variant, intron_variant	Intron 5 of 5		NP_001243098.1
APOM	NR_045828.2	n.582+7G>T		splice_region_variant, intron_variant	Intron 5 of 5
APOM	XM_006715150.4	c.445+7G>T		splice_region_variant, intron_variant	Intron 5 of 5		XP_006715213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOM	ENST00000375916.4	c.541+7G>T		splice_region_variant, intron_variant	Intron 5 of 5	1	NM_019101.3	ENSP00000365081.3
APOM	ENST00000375920.8	c.325+7G>T		splice_region_variant, intron_variant	Intron 5 of 5	1		ENSP00000365085.4
APOM	ENST00000375918.6	c.332G>T	p.Gly111Val	missense_variant	Exon 5 of 5	2		ENSP00000365083.2

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21322 AN: 151976 Hom.: 2539 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.0814

Gnomad FIN AF: 0.00680

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.0550

Gnomad OTH AF: 0.176

GnomAD2 exomes AF: 0.0931 AC: 23033 AN: 247410 AF XY: 0.0868

Gnomad AFR exome AF: 0.321

Gnomad AMR exome AF: 0.127

Gnomad ASJ exome AF: 0.192

Gnomad EAS exome AF: 0.160

Gnomad FIN exome AF: 0.00634

Gnomad NFE exome AF: 0.0534

Gnomad OTH exome AF: 0.104

GnomAD4 exome AF: 0.0669 AC: 97355 AN: 1454528 Hom.: 5667 Cov.: 30 AF XY: 0.0664 AC XY: 48081 AN XY: 724102

African (AFR) AF: 0.326 AC: 10836 AN: 33248

American (AMR) AF: 0.130 AC: 5833 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 5024 AN: 26048

East Asian (EAS) AF: 0.151 AC: 5996 AN: 39660

South Asian (SAS) AF: 0.0728 AC: 6271 AN: 86124

European-Finnish (FIN) AF: 0.00801 AC: 423 AN: 52822

Middle Eastern (MID) AF: 0.217 AC: 1246 AN: 5750

European-Non Finnish (NFE) AF: 0.0504 AC: 55790 AN: 1106022

Other (OTH) AF: 0.0987 AC: 5936 AN: 60148

GnomAD4 genome AF: 0.140 AC: 21355 AN: 152094 Hom.: 2549 Cov.: 32 AF XY: 0.138 AC XY: 10267 AN XY: 74368

African (AFR) AF: 0.317 AC: 13149 AN: 41436

American (AMR) AF: 0.137 AC: 2088 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 666 AN: 3472

East Asian (EAS) AF: 0.154 AC: 799 AN: 5178

South Asian (SAS) AF: 0.0808 AC: 390 AN: 4826

European-Finnish (FIN) AF: 0.00680 AC: 72 AN: 10586

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.0550 AC: 3739 AN: 67996

Other (OTH) AF: 0.176 AC: 372 AN: 2108

Alfa AF: 0.0943 Hom.: 2656

Bravo AF: 0.159

TwinsUK AF: 0.0472 AC: 175

ALSPAC AF: 0.0488 AC: 188

ESP6500AA AF: 0.306 AC: 925

ESP6500EA AF: 0.0596 AC: 323

ExAC AF: 0.0913 AC: 10982

Asia WGS AF: 0.122 AC: 425 AN: 3478

EpiCase AF: 0.0667

EpiControl AF: 0.0695

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	7.1
DANN	Benign	0.67
DEOGEN2	Benign	0.022	T
Eigen	Benign	0.18
Eigen_PC	Benign	-0.063
FATHMM_MKL	Benign	0.52	D
MetaRNN	Benign	0.0012	T
MetaSVM	Benign	-0.96	T
PhyloP100		0.86
PROVEAN	Benign	0.82	N
REVEL	Benign	0.019
Sift	Pathogenic	0.0	D
Vest4		0.087
ClinPred		0.065	T
GERP RS		2.7
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000020
dbscSNV1_RF	Benign	0.010
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

Other links and lift over

dbSNP: rs707922; hg19: chr6-31625507; COSMIC: COSV65524044; COSMIC: COSV65524044;