11-67438398-C-G

Variant names:

• chr11-67438398-C-G
• rs143727296
• NM_020441.3:c.1448G>C

Variant summary

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

The NM_020441.3(CORO1B):​c.1448G>C​(p.Arg483Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,455,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R483H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CORO1B NM_020441.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.472
• Publications: 0 publications found

Genes affected

CORO1B (HGNC:2253): (coronin 1B) Members of the coronin family, such as CORO1B, are WD repeat-containing actin-binding proteins that regulate cell motility (Cai et al., 2005 [PubMed 16027158]).[supplied by OMIM, Mar 2008]

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=0.21604142).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020441.3. 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
	CORO1B	NM_020441.3	MANE Select	c.1448G>C	p.Arg483Pro	missense	Exon 11 of 11	NP_065174.1	Q9BR76
	CORO1B	NM_001018070.3		c.1448G>C	p.Arg483Pro	missense	Exon 12 of 12	NP_001018080.1	Q9BR76

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORO1B	ENST00000341356.10	TSL:1 MANE Select	c.1448G>C	p.Arg483Pro	missense	Exon 11 of 11	ENSP00000340211.5	Q9BR76
	CORO1B	ENST00000955904.1		c.1487G>C	p.Arg496Pro	missense	Exon 11 of 11	ENSP00000625963.1
	CORO1B	ENST00000393893.5	TSL:5	c.1448G>C	p.Arg483Pro	missense	Exon 12 of 12	ENSP00000377471.1	Q9BR76

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000820 AC: 2 AN: 243940 AF XY: 0.00

Gnomad AFR exome AF: 0.000126

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1455470 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 723208

African (AFR) AF: 0.0000898 AC: 3 AN: 33418

American (AMR) AF: 0.00 AC: 0 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26040

East Asian (EAS) AF: 0.00 AC: 0 AN: 39530

South Asian (SAS) AF: 0.00 AC: 0 AN: 86100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51426

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108554

Other (OTH) AF: 0.00 AC: 0 AN: 60082

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.47
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.17
Sift	Benign	0.034	D
Sift4G	Benign	0.21	T
Polyphen		0.87	P
Vest4		0.35
MutPred		0.22		Loss of MoRF binding (P = 0.0241)
MVP		0.81
MPC		1.1
ClinPred		0.40	T
GERP RS		4.8
Varity_R		0.67
gMVP		0.43
Mutation Taster		=70/30	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

dbSNP: rs143727296; hg19: chr11-67205869;