3-195573869-C-T

Variant names:

• chr3-195573869-C-T
• rs76929107
• NM_001647.4:c.226G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001647.4(APOD):​c.226G>A​(p.Val76Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,614,200 control chromosomes in the GnomAD database, including 166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0092 (15 hom., cov: 32)
  • Exomes 𝑓: 0.012 (151 hom.)
• Consequence: APOD NM_001647.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.46
• Publications: 17 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00900656).
• BP6: Variant 3-195573869-C-T is Benign according to our data. Variant chr3-195573869-C-T is described in ClinVar as Benign. ClinVar VariationId is 2654366.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 15 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.226G>A	p.Val76Met	missense	Exon 3 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.226G>A	p.Val76Met	missense	Exon 3 of 5	ENSP00000345179.3	P05090
	APOD	ENST00000421243.5	TSL:3	c.310G>A	p.Val104Met	missense	Exon 4 of 6	ENSP00000415235.1	C9JF17
	APOD	ENST00000953531.1		c.292G>A	p.Val98Met	missense	Exon 4 of 6	ENSP00000623590.1

Frequencies

GnomAD3 genomes AF: 0.00918 AC: 1397 AN: 152230 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.00239

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00648

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0175

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0137

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00953 AC: 2395 AN: 251418 AF XY: 0.00967

Gnomad AFR exome AF: 0.00191

Gnomad AMR exome AF: 0.00561

Gnomad ASJ exome AF: 0.0104

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0167

Gnomad NFE exome AF: 0.0135

Gnomad OTH exome AF: 0.0135

GnomAD4 exome AF: 0.0120 AC: 17497 AN: 1461852 Hom.: 151 Cov.: 33 AF XY: 0.0117 AC XY: 8527 AN XY: 727232

African (AFR) AF: 0.00176 AC: 59 AN: 33480

American (AMR) AF: 0.00608 AC: 272 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00987 AC: 258 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00238 AC: 205 AN: 86258

European-Finnish (FIN) AF: 0.0163 AC: 871 AN: 53418

Middle Eastern (MID) AF: 0.00451 AC: 26 AN: 5768

European-Non Finnish (NFE) AF: 0.0136 AC: 15160 AN: 1111984

Other (OTH) AF: 0.0107 AC: 646 AN: 60394

GnomAD4 genome AF: 0.00917 AC: 1397 AN: 152348 Hom.: 15 Cov.: 32 AF XY: 0.00969 AC XY: 722 AN XY: 74496

African (AFR) AF: 0.00238 AC: 99 AN: 41586

American (AMR) AF: 0.00647 AC: 99 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4830

European-Finnish (FIN) AF: 0.0175 AC: 186 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0137 AC: 935 AN: 68024

Other (OTH) AF: 0.0104 AC: 22 AN: 2116

Alfa AF: 0.0122 Hom.: 53

Bravo AF: 0.00811

TwinsUK AF: 0.0140 AC: 52

ALSPAC AF: 0.0174 AC: 67

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.0140 AC: 120

ExAC AF: 0.0101 AC: 1226

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.0139

EpiControl AF: 0.0130

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	T
MetaRNN	Benign	0.0090	T
MetaSVM	Uncertain	0.22	D
MutationAssessor	Pathogenic	3.9	H
PhyloP100		3.5
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.81
MPC		0.60
ClinPred		0.075	T
GERP RS		5.7
Varity_R		0.87
gMVP		0.68
Mutation Taster		=50/50

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: rs76929107; hg19: chr3-195300740; COSMIC: COSV99070336;