rs1801692

Variant names:

• chr17-66226046-C-T
• rs1801692
• NM_000042.3:c.320G>A

Variant summary

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

The NM_000042.3(APOH):​c.320G>A​(p.Ser107Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0422 in 1,611,824 control chromosomes in the GnomAD database, including 1,557 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.035 (128 hom., cov: 33)
  • Exomes 𝑓: 0.043 (1429 hom.)
• Consequence: APOH NM_000042.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.568
• Publications: 25 publications found

Genes affected

APOH (HGNC:616): (apolipoprotein H) Apolipoprotein H, also known as beta-2-glycoprotein I, is a component of circulating plasma lipoproteins. It has been implicated in a variety of physiologic pathways including lipoprotein metabolism, coagulation, hemostasis, and the production of antiphospholipid autoantibodies. APOH may be a required cofactor for anionic phospholipid binding by the antiphospholipid autoantibodies found in sera of many patients with lupus and primary antiphospholipid syndrome (APS). The anti-beta (2) glycoprotein I antibodies from APS patients, mediate inhibition of activated protein C which has anticoagulant properties. Because beta-2-GPI is the main autoantigen in patients with APS, the disruption of this pathway by autoantibodies may be an important mechanism for thrombosis in patients with APS.[provided by RefSeq, Dec 2019]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023064613).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOH	NM_000042.3	c.320G>A	p.Ser107Asn	missense_variant	Exon 3 of 8	ENST00000205948.11	NP_000033.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOH	ENST00000205948.11	c.320G>A	p.Ser107Asn	missense_variant	Exon 3 of 8	1	NM_000042.3	ENSP00000205948.6
APOH	ENST00000581797.5	c.140G>A	p.Ser47Asn	missense_variant	Exon 3 of 6	3		ENSP00000463553.1
APOH	ENST00000577982.1	c.320G>A	p.Ser107Asn	missense_variant	Exon 4 of 6	5		ENSP00000464301.1

Frequencies

GnomAD3 genomes AF: 0.0346 AC: 5257 AN: 152072 Hom.: 128 Cov.: 33

Gnomad AFR AF: 0.0134

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0277

Gnomad ASJ AF: 0.0550

Gnomad EAS AF: 0.0260

Gnomad SAS AF: 0.0544

Gnomad FIN AF: 0.0392

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0451

Gnomad OTH AF: 0.0363

GnomAD2 exomes AF: 0.0389 AC: 9723 AN: 250016 AF XY: 0.0413

Gnomad AFR exome AF: 0.0121

Gnomad AMR exome AF: 0.0175

Gnomad ASJ exome AF: 0.0524

Gnomad EAS exome AF: 0.0249

Gnomad FIN exome AF: 0.0364

Gnomad NFE exome AF: 0.0462

Gnomad OTH exome AF: 0.0403

GnomAD4 exome AF: 0.0430 AC: 62702 AN: 1459634 Hom.: 1429 Cov.: 30 AF XY: 0.0437 AC XY: 31741 AN XY: 726046

African (AFR) AF: 0.0130 AC: 436 AN: 33418

American (AMR) AF: 0.0181 AC: 805 AN: 44518

Ashkenazi Jewish (ASJ) AF: 0.0549 AC: 1431 AN: 26084

East Asian (EAS) AF: 0.0150 AC: 593 AN: 39662

South Asian (SAS) AF: 0.0558 AC: 4775 AN: 85634

European-Finnish (FIN) AF: 0.0369 AC: 1969 AN: 53388

Middle Eastern (MID) AF: 0.0568 AC: 327 AN: 5762

European-Non Finnish (NFE) AF: 0.0448 AC: 49800 AN: 1110850

Other (OTH) AF: 0.0425 AC: 2566 AN: 60318

GnomAD4 genome AF: 0.0345 AC: 5258 AN: 152190 Hom.: 128 Cov.: 33 AF XY: 0.0343 AC XY: 2555 AN XY: 74398

African (AFR) AF: 0.0133 AC: 554 AN: 41538

American (AMR) AF: 0.0276 AC: 422 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0550 AC: 191 AN: 3472

East Asian (EAS) AF: 0.0258 AC: 134 AN: 5184

South Asian (SAS) AF: 0.0550 AC: 265 AN: 4816

European-Finnish (FIN) AF: 0.0392 AC: 415 AN: 10582

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0451 AC: 3067 AN: 68002

Other (OTH) AF: 0.0364 AC: 77 AN: 2116

Alfa AF: 0.0415 Hom.: 602

Bravo AF: 0.0323

TwinsUK AF: 0.0453 AC: 168

ALSPAC AF: 0.0444 AC: 171

ESP6500AA AF: 0.0154 AC: 68

ESP6500EA AF: 0.0455 AC: 391

ExAC AF: 0.0405 AC: 4921

Asia WGS AF: 0.0560 AC: 193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	2.2
DANN	Benign	0.51
DEOGEN2	Benign	0.080	T;.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.43	T;T;T
MetaRNN	Benign	0.0023	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.19	N;.;.
PhyloP100		-0.57
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.070	N;.;.
REVEL	Benign	0.054
Sift	Benign	1.0	T;.;.
Sift4G	Benign	0.93	T;.;.
Polyphen		0.0	B;.;.
Vest4		0.039
MPC		0.14
ClinPred		0.000017	T
GERP RS		-2.3
Varity_R		0.27
gMVP		0.34
Mutation Taster		=92/8	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: rs1801692; hg19: chr17-64222164; COSMIC: COSV52771946;