rs707921

Variant names:

• chr6-31657764-C-A
• rs707921
• NM_019101.3:c.541+41C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-31657764-C-A
• chr6-31657764-C-G
• chr6-31657764-C-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+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
• Publications: 29 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 (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 rank	MANE	Protein	UniProt
APOM	NM_019101.3	c.541+41C>A		intron_variant	Intron 5 of 5	ENST00000375916.4	NP_061974.2
APOM	NM_001256169.2	c.325+41C>A		intron_variant	Intron 5 of 5		NP_001243098.1
APOM	NR_045828.2	n.582+41C>A		intron_variant	Intron 5 of 5
APOM	XM_006715150.4	c.445+41C>A		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+41C>A		intron_variant	Intron 5 of 5	1	NM_019101.3	ENSP00000365081.3
APOM	ENST00000375920.8	c.325+41C>A		intron_variant	Intron 5 of 5	1		ENSP00000365085.4
APOM	ENST00000375918.6	c.366C>A	p.Thr122Thr	synonymous_variant	Exon 5 of 5	2		ENSP00000365083.2

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

GnomAD2 exomes AF: 0.0570 AC: 14126 AN: 247858 AF XY: 0.0540

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 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

African (AFR) AF: 0.208 AC: 6585 AN: 31718

American (AMR) AF: 0.0725 AC: 3237 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.0519 AC: 1330 AN: 25602

East Asian (EAS) AF: 0.106 AC: 4149 AN: 39312

South Asian (SAS) AF: 0.0553 AC: 4677 AN: 84644

European-Finnish (FIN) AF: 0.00521 AC: 277 AN: 53204

Middle Eastern (MID) AF: 0.143 AC: 807 AN: 5628

European-Non Finnish (NFE) AF: 0.0307 AC: 32066 AN: 1043908

Other (OTH) AF: 0.0579 AC: 3348 AN: 57796

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

African (AFR) AF: 0.201 AC: 8329 AN: 41456

American (AMR) AF: 0.0764 AC: 1167 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0507 AC: 176 AN: 3472

East Asian (EAS) AF: 0.137 AC: 708 AN: 5176

South Asian (SAS) AF: 0.0624 AC: 301 AN: 4824

European-Finnish (FIN) AF: 0.00481 AC: 51 AN: 10612

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0312 AC: 2122 AN: 68010

Other (OTH) AF: 0.0964 AC: 203 AN: 2106

Alfa AF: 0.0531 Hom.: 1730

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
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs707921; hg19: chr6-31625541; COSMIC: COSV65524048; COSMIC: COSV65524048;