NM_018690.4:c.610G>A

Variant names:

• chr16-28495651-G-A
• NM_018690.4:c.610G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_018690.4(APOBR):​c.610G>A​(p.Gly204Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,397,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: APOBR NM_018690.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.04
• Publications: 0 publications found

Genes affected

APOBR (HGNC:24087): (apolipoprotein B receptor) Apolipoprotein B48 receptor is a macrophage receptor that binds to the apolipoprotein B48 of dietary triglyceride (TG)-rich lipoproteins. This receptor may provide essential lipids, lipid-soluble vitamins and other nutrients to reticuloendothelial cells. If overwhelmed with elevated plasma triglyceride, the apolipoprotein B48 receptor may contribute to foam cell formation, endothelial dysfunction, and atherothrombogenesis. [provided by RefSeq, Jul 2008]

CLN3 (HGNC:2074): (CLN3 lysosomal/endosomal transmembrane protein, battenin) This gene encodes a protein that is involved in lysosomal function. Mutations in this, as well as other neuronal ceroid-lipofuscinosis (CLN) genes, cause neurodegenerative diseases commonly known as Batten disease or collectively known as neuronal ceroid lipofuscinoses (NCLs). Many alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

CLN3 Gene-Disease associations (from GenCC):

• inherited retinal dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• neuronal ceroid lipofuscinosis

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• neuronal ceroid lipofuscinosis 3

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Genomics England PanelApp, G2P, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.023701549).
• BP6: Variant 16-28495651-G-A is Benign according to our data. Variant chr16-28495651-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2227056.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018690.4. 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
	APOBR	NM_018690.4	MANE Select	c.610G>A	p.Gly204Arg	missense	Exon 2 of 4	NP_061160.3	Q0VD83-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBR	ENST00000564831.6	TSL:1 MANE Select	c.610G>A	p.Gly204Arg	missense	Exon 2 of 4	ENSP00000457539.1	Q0VD83-4
	APOBR	ENST00000875807.1		c.610G>A	p.Gly204Arg	missense	Exon 2 of 4	ENSP00000545866.1
	CLN3	ENST00000569430.7	TSL:5	c.-2429C>T		upstream_gene	N/A	ENSP00000454229.1	Q13286-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1397704 Hom.: 0 Cov.: 76 AF XY: 0.00000145 AC XY: 1 AN XY: 688862

African (AFR) AF: 0.0000314 AC: 1 AN: 31860

American (AMR) AF: 0.00 AC: 0 AN: 35386

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24800

East Asian (EAS) AF: 0.00 AC: 0 AN: 36154

South Asian (SAS) AF: 0.00 AC: 0 AN: 79072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 0.00000186 AC: 2 AN: 1077608

Other (OTH) AF: 0.00 AC: 0 AN: 58074

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.0020
DANN	Benign	0.76
DEOGEN2	Benign	0.00065	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.4	N
PhyloP100		-3.0
PrimateAI	Benign	0.22	T
PROVEAN	Benign	1.5	N
REVEL	Benign	0.022
Sift	Benign	0.91	T
Sift4G	Benign	0.57	T
Vest4		0.039
MutPred		0.13		Gain of MoRF binding (P = 0.014)
MVP		0.24
MPC		0.070
ClinPred		0.042	T
GERP RS		-4.6
PromoterAI		0.036	Neutral
Varity_R		0.048
gMVP		0.0039

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

hg19: chr16-28506972;