4-54064254-C-T

Variant names:

• chr4-54064254-C-T
• NM_012110.4:c.47G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012110.4(CHIC2):​c.47G>A​(p.Arg16Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CHIC2 NM_012110.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.75

Genes affected

CHIC2 (HGNC:1935): (cysteine rich hydrophobic domain 2) This gene encodes a member of the CHIC family of proteins. The encoded protein contains a cysteine-rich hydrophobic (CHIC) motif, and is localized to vesicular structures and the plasma membrane. This gene is associated with some cases of acute myeloid leukemia. [provided by RefSeq, Jul 2008]

ENSG00000282278 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.124385685).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHIC2	NM_012110.4	c.47G>A	p.Arg16Gln	missense_variant	Exon 1 of 6	ENST00000263921.8	NP_036242.1
CHIC2	XM_006714037.5	c.47G>A	p.Arg16Gln	missense_variant	Exon 1 of 6		XP_006714100.1
CHIC2	XM_011534382.3	c.47G>A	p.Arg16Gln	missense_variant	Exon 1 of 4		XP_011532684.1
CHIC2	XM_047450063.1	c.11+1050G>A		intron_variant	Intron 2 of 6		XP_047306019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHIC2	ENST00000263921.8	c.47G>A	p.Arg16Gln	missense_variant	Exon 1 of 6	1	NM_012110.4	ENSP00000263921.3
ENSG00000282278	ENST00000507166.5	c.1018-210671C>T		intron_variant	Intron 12 of 23	2		ENSP00000423325.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.47G>A (p.R16Q) alteration is located in exon 1 (coding exon 1) of the CHIC2 gene. This alteration results from a G to A substitution at nucleotide position 47, causing the arginine (R) at amino acid position 16 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.089	T;T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.040
FATHMM_MKL	Benign	0.51	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.12	N;N
REVEL	Benign	0.073
Sift	Benign	0.48	T;T
Sift4G	Benign	0.58	T;T
Polyphen		0.25	B;.
Vest4		0.36
MutPred		0.19		Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);
MVP		0.16
MPC		0.98
ClinPred		0.92	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.80

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-54930421;