4-48857324-C-T

Variant names:

• chr4-48857324-C-T
• NM_017830.4:c.659C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017830.4(OCIAD1):​c.659C>T​(p.Pro220Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,441,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: OCIAD1 NM_017830.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.79
• Publications: 0 publications found

Genes affected

OCIAD1 (HGNC:16074): (OCIA domain containing 1) Predicted to be involved in several processes, including hematopoietic stem cell homeostasis; positive regulation of receptor signaling pathway via JAK-STAT; and regulation of stem cell differentiation. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

OCIAD1-AS1 (HGNC:40751): (OCIAD1 antisense RNA 1)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14821899).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017830.4. 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
	OCIAD1	NM_017830.4	MANE Select	c.659C>T	p.Pro220Leu	missense	Exon 8 of 9	NP_060300.1	Q9NX40-1
	OCIAD1	NM_001168254.2		c.674C>T	p.Pro225Leu	missense	Exon 8 of 9	NP_001161726.1
	OCIAD1	NM_001079839.3		c.659C>T	p.Pro220Leu	missense	Exon 8 of 9	NP_001073308.1	Q9NX40-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCIAD1	ENST00000264312.12	TSL:1 MANE Select	c.659C>T	p.Pro220Leu	missense	Exon 8 of 9	ENSP00000264312.7	Q9NX40-1
	OCIAD1	ENST00000381473.7	TSL:1	c.659C>T	p.Pro220Leu	missense	Exon 8 of 9	ENSP00000370882.3	Q9NX40-1
	OCIAD1	ENST00000396448.6	TSL:1	c.*29-3401C>T		intron	N/A	ENSP00000379725.2	Q9NX40-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441200 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 717148

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000308 AC: 1 AN: 32518

American (AMR) AF: 0.00 AC: 0 AN: 42516

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25564

East Asian (EAS) AF: 0.00 AC: 0 AN: 38798

South Asian (SAS) AF: 0.00 AC: 0 AN: 82734

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52652

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101302

Other (OTH) AF: 0.00 AC: 0 AN: 59424

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

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	0.076
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.8
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.066
Sift	Benign	0.27	T
Sift4G	Benign	0.67	T
Polyphen		0.85	P
Vest4		0.31
MutPred		0.23		Gain of glycosylation at S221 (P = 0.0154)
MVP		0.50
MPC		0.14
ClinPred		0.68	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.083
gMVP		0.29
Mutation Taster		=91/9	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

hg19: chr4-48859341;