12-108658818-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_014325.4(CORO1C):c.550C>T(p.Arg184Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000892 in 1,613,704 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 0.000085 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000090 (0 hom.)
• Consequence: CORO1C NM_014325.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.81

Genes affected

CORO1C (HGNC:2254): (coronin 1C) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Feb 2013]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13694468).
• BS2: High AC in GnomAd at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CORO1C	NM_014325.4	c.550C>T	p.Arg184Trp	missense_variant	5/11	ENST00000261401.8
CORO1C	NM_001105237.2	c.709C>T	p.Arg237Trp	missense_variant	5/11
CORO1C	NM_001276471.2	c.550C>T	p.Arg184Trp	missense_variant	5/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CORO1C	ENST00000261401.8	c.550C>T	p.Arg184Trp	missense_variant	5/11	1	NM_014325.4	P1

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152168 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000151 AC: 38 AN: 251486 Hom.: 0 AF XY: 0.000169 AC XY: 23 AN XY: 135918

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000751

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000896 AC: 131 AN: 1461418 Hom.: 0 Cov.: 31 AF XY: 0.0000963 AC XY: 70 AN XY: 727032

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000639

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152286 Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7 AN XY: 74452

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000131 Hom.: 1

Bravo AF: 0.0000718

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000148 AC: 18

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 30, 2023

The c.550C>T (p.R184W) alteration is located in exon 5 (coding exon 4) of the CORO1C gene. This alteration results from a C to T substitution at nucleotide position 550, causing the arginine (R) at amino acid position 184 to be replaced by a tryptophan (W). 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	0.13
BayesDel_addAF	Benign	0.0043	T
BayesDel_noAF	Pathogenic	0.14
Cadd	Uncertain	25
Dann	Benign	0.93
DEOGEN2	Benign	0.025	T;.;T;T;.;T
Eigen	Benign	0.021
Eigen_PC	Benign	0.11
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.14	T;T;T;T;T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.9	L;.;L;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	1.4	N;N;N;N;N;N
REVEL	Uncertain	0.30
Sift	Benign	0.32	T;T;T;T;T;T
Sift4G	Benign	0.22	T;T;T;T;T;.
Polyphen		0.24	B;.;B;.;.;.
Vest4		0.73
MVP		0.66
MPC		0.70
ClinPred		0.080	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.22
gMVP		0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs143115944; hg19: chr12-109052594;