rs5952

Variant names:

• chr3-195579418-A-G
• rs5952
• NM_001647.4:c.44T>C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001647.4(APOD):​c.44T>C​(p.Phe15Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00461 in 1,614,068 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0047 (28 hom.)
• Consequence: APOD NM_001647.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.31
• Publications: 13 publications found

Genes affected

APOD (HGNC:612): (apolipoprotein D) This gene encodes a component of high density lipoprotein that has no marked similarity to other apolipoprotein sequences. It has a high degree of homology to plasma retinol-binding protein and other members of the alpha 2 microglobulin protein superfamily of carrier proteins, also known as lipocalins. This glycoprotein is closely associated with the enzyme lecithin:cholesterol acyltransferase - an enzyme involved in lipoprotein metabolism. [provided by RefSeq, Aug 2008]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0046077073).
• BP6: Variant 3-195579418-A-G is Benign according to our data. Variant chr3-195579418-A-G is described in ClinVar as Benign. ClinVar VariationId is 769625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001647.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOD	NM_001647.4	MANE Select	c.44T>C	p.Phe15Ser	missense	Exon 2 of 5	NP_001638.1	P05090

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOD	ENST00000343267.8	TSL:1 MANE Select	c.44T>C	p.Phe15Ser	missense	Exon 2 of 5	ENSP00000345179.3	P05090
	APOD	ENST00000421243.5	TSL:3	c.128T>C	p.Phe43Ser	missense	Exon 3 of 6	ENSP00000415235.1	C9JF17
	APOD	ENST00000953531.1		c.44T>C	p.Phe15Ser	missense	Exon 3 of 6	ENSP00000623590.1

Frequencies

GnomAD3 genomes AF: 0.00421 AC: 641 AN: 152212 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00635

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00678

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00578

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00422 AC: 1056 AN: 250390 AF XY: 0.00451

Gnomad AFR exome AF: 0.000820

Gnomad AMR exome AF: 0.00416

Gnomad ASJ exome AF: 0.000796

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00752

Gnomad NFE exome AF: 0.00593

Gnomad OTH exome AF: 0.00637

GnomAD4 exome AF: 0.00465 AC: 6802 AN: 1461738 Hom.: 28 Cov.: 31 AF XY: 0.00455 AC XY: 3310 AN XY: 727178

African (AFR) AF: 0.000657 AC: 22 AN: 33480

American (AMR) AF: 0.00458 AC: 205 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000689 AC: 18 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000661 AC: 57 AN: 86258

European-Finnish (FIN) AF: 0.00711 AC: 379 AN: 53310

Middle Eastern (MID) AF: 0.00711 AC: 41 AN: 5768

European-Non Finnish (NFE) AF: 0.00523 AC: 5813 AN: 1111978

Other (OTH) AF: 0.00442 AC: 267 AN: 60386

GnomAD4 genome AF: 0.00421 AC: 641 AN: 152330 Hom.: 3 Cov.: 33 AF XY: 0.00443 AC XY: 330 AN XY: 74482

African (AFR) AF: 0.00108 AC: 45 AN: 41576

American (AMR) AF: 0.00634 AC: 97 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4828

European-Finnish (FIN) AF: 0.00678 AC: 72 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00578 AC: 393 AN: 68024

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.00507 Hom.: 4

Bravo AF: 0.00371

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00467 AC: 18

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00628 AC: 54

ExAC AF: 0.00417 AC: 506

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00687

EpiControl AF: 0.00735

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	APOD-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		2.3
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.19
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.25	T
Polyphen		0.0020	B
Vest4		0.31
MVP		0.33
MPC		0.23
ClinPred		0.036	T
GERP RS		1.6
Varity_R		0.14
gMVP		0.40
Mutation Taster		=99/1	polymorphism

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: rs5952; hg19: chr3-195306289;