chr4-48885525-C-T

Variant names:

• chr4-48885525-C-T
• rs147751611
• NM_001014446.3:c.424G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001014446.3(OCIAD2):​c.424G>A​(p.Gly142Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000514 in 1,611,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00042 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00052 (0 hom.)
• Consequence: OCIAD2 NM_001014446.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.39
• Publications: 2 publications found

Genes affected

OCIAD2 (HGNC:28685): (OCIA domain containing 2) Predicted to be involved in endocytosis; hematopoietic stem cell homeostasis; and positive regulation of receptor signaling pathway via JAK-STAT. Predicted to act upstream of or within response to bacterium. Predicted to be located in Golgi apparatus; endosome; and lysosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001014446.3. 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
	OCIAD2	NM_001014446.3	MANE Select	c.424G>A	p.Gly142Arg	missense	Exon 7 of 7	NP_001014446.1	Q56VL3-1
	OCIAD2	NM_001286774.2		c.238G>A	p.Gly80Arg	missense	Exon 6 of 6	NP_001273703.1
	OCIAD2	NM_001286773.2		c.*6G>A		3_prime_UTR	Exon 6 of 6	NP_001273702.1	Q56VL3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCIAD2	ENST00000508632.6	TSL:1 MANE Select	c.424G>A	p.Gly142Arg	missense	Exon 7 of 7	ENSP00000423014.1	Q56VL3-1
	OCIAD2	ENST00000273860.8	TSL:1	c.*6G>A		3_prime_UTR	Exon 6 of 6	ENSP00000273860.4	Q56VL3-2
	OCIAD2	ENST00000514576.5	TSL:1	n.1743G>A		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes AF: 0.000420 AC: 64 AN: 152200 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000549 AC: 138 AN: 251204 AF XY: 0.000552

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000521

Gnomad ASJ exome AF: 0.00348

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000590

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000523 AC: 764 AN: 1459680 Hom.: 0 Cov.: 28 AF XY: 0.000519 AC XY: 377 AN XY: 726346

African (AFR) AF: 0.0000897 AC: 3 AN: 33434

American (AMR) AF: 0.000559 AC: 25 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00353 AC: 92 AN: 26090

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39670

South Asian (SAS) AF: 0.000418 AC: 36 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5764

European-Non Finnish (NFE) AF: 0.000506 AC: 562 AN: 1110038

Other (OTH) AF: 0.000597 AC: 36 AN: 60342

GnomAD4 genome AF: 0.000420 AC: 64 AN: 152200 Hom.: 0 Cov.: 33 AF XY: 0.000363 AC XY: 27 AN XY: 74356

African (AFR) AF: 0.0000965 AC: 4 AN: 41450

American (AMR) AF: 0.000458 AC: 7 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68040

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000767 Hom.: 0

Bravo AF: 0.000499

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000544 AC: 66

EpiCase AF: 0.000873

EpiControl AF: 0.000771

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.10
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.0087
Eigen_PC	Benign	0.0063
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		2.4
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.051
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.020	D
Polyphen		0.84	P
Vest4		0.24
MutPred		0.13		Gain of solvent accessibility (P = 0.019)
MVP		0.28
MPC		0.26
ClinPred		0.045	T
GERP RS		5.3
Varity_R		0.067
gMVP		0.45
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.37		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.37		Position offset: 40

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs147751611; hg19: chr4-48887542; COSMIC: COSV99060662;