chr2-42763085-C-G

Variant names:

• chr2-42763085-C-G
• rs143944527
• NM_148962.5:c.978G>C

Variant summary

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

The NM_148962.5(OXER1):​c.978G>C​(p.Gln326His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00545 in 1,614,148 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0056 (31 hom.)
• Consequence: OXER1 NM_148962.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0190
• Publications: 10 publications found

Genes affected

OXER1 (HGNC:24884): (oxoeicosanoid receptor 1) Enables G protein-coupled receptor activity and icosanoid binding activity. Involved in adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0049654245).
• BP6: Variant 2-42763085-C-G is Benign according to our data. Variant chr2-42763085-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3341549.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_148962.5. 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
	OXER1	NM_148962.5	MANE Select	c.978G>C	p.Gln326His	missense	Exon 1 of 1	NP_683765.2	Q8TDS5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OXER1	ENST00000378661.4	TSL:6 MANE Select	c.978G>C	p.Gln326His	missense	Exon 1 of 1	ENSP00000367930.3	Q8TDS5

Frequencies

GnomAD3 genomes AF: 0.00393 AC: 598 AN: 152208 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000989

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00641

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00645

Gnomad OTH AF: 0.00573

GnomAD2 exomes AF: 0.00374 AC: 936 AN: 250282 AF XY: 0.00363

Gnomad AFR exome AF: 0.000955

Gnomad AMR exome AF: 0.00448

Gnomad ASJ exome AF: 0.00109

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00638

Gnomad OTH exome AF: 0.00378

GnomAD4 exome AF: 0.00560 AC: 8193 AN: 1461822 Hom.: 31 Cov.: 35 AF XY: 0.00544 AC XY: 3958 AN XY: 727220

African (AFR) AF: 0.000956 AC: 32 AN: 33480

American (AMR) AF: 0.00436 AC: 195 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00111 AC: 29 AN: 26134

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

South Asian (SAS) AF: 0.000278 AC: 24 AN: 86258

European-Finnish (FIN) AF: 0.000300 AC: 16 AN: 53356

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.00686 AC: 7629 AN: 1112006

Other (OTH) AF: 0.00435 AC: 263 AN: 60396

GnomAD4 genome AF: 0.00393 AC: 598 AN: 152326 Hom.: 2 Cov.: 33 AF XY: 0.00360 AC XY: 268 AN XY: 74486

African (AFR) AF: 0.000986 AC: 41 AN: 41578

American (AMR) AF: 0.00640 AC: 98 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00645 AC: 439 AN: 68030

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.00532 Hom.: 1

Bravo AF: 0.00434

TwinsUK AF: 0.00593 AC: 22

ALSPAC AF: 0.00649 AC: 25

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.00500 AC: 43

ExAC AF: 0.00344 AC: 417

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00627

EpiControl AF: 0.00664

ClinVar

ClinVar submissions

Significance: Likely 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	Benign	0.14
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.0050	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.019
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.096
Sift	Benign	0.52	T
Sift4G	Uncertain	0.043	D
Polyphen		0.99	D
Vest4		0.29
MutPred		0.48		Gain of catalytic residue at Q365 (P = 0.0315)
MVP		0.61
MPC		0.21
ClinPred		0.012	T
GERP RS		3.1
Varity_R		0.14
gMVP		0.24
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs143944527; hg19: chr2-42990225; COSMIC: COSV54311891; COSMIC: COSV54311891;