rs150857828

Variant names:

• chr16-30188392-C-A
• rs150857828
• NM_007074.4:c.1097C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_007074.4(CORO1A):​c.1097C>A​(p.Pro366His) variant causes a missense change. The variant allele was found at a frequency of 0.00295 in 1,613,852 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P366P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0025 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0030 (14 hom.)
• Consequence: CORO1A NM_007074.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 6.75
• Publications: 9 publications found

Genes affected

CORO1A (HGNC:2252): (coronin 1A) 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. Alternative splicing results in multiple transcript variants. A related pseudogene has been defined on chromosome 16. [provided by RefSeq, Sep 2010]

CORO1A Gene-Disease associations (from GenCC):

• severe combined immunodeficiency due to CORO1A deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• epidermodysplasia verruciformis

  Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01099515).
• BP6: Variant 16-30188392-C-A is Benign according to our data. Variant chr16-30188392-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 541422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00253 (386/152302) while in subpopulation NFE AF = 0.00354 (241/68022). AF 95% confidence interval is 0.00318. There are 0 homozygotes in GnomAd4. There are 169 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 14 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007074.4. 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
	CORO1A	NM_007074.4	MANE Select	c.1097C>A	p.Pro366His	missense	Exon 10 of 11	NP_009005.1	P31146
	CORO1A	NM_001193333.3		c.1097C>A	p.Pro366His	missense	Exon 11 of 12	NP_001180262.1	P31146

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORO1A	ENST00000219150.10	TSL:1 MANE Select	c.1097C>A	p.Pro366His	missense	Exon 10 of 11	ENSP00000219150.6	P31146
	CORO1A	ENST00000570045.5	TSL:1	c.1097C>A	p.Pro366His	missense	Exon 11 of 12	ENSP00000455552.1	P31146
	CORO1A	ENST00000891502.1		c.1097C>A	p.Pro366His	missense	Exon 11 of 12	ENSP00000561561.1

Frequencies

GnomAD3 genomes AF: 0.00254 AC: 386 AN: 152184 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00254

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00354

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00301 AC: 752 AN: 250000 AF XY: 0.00301

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.000665

Gnomad ASJ exome AF: 0.0213

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00254

Gnomad NFE exome AF: 0.00384

Gnomad OTH exome AF: 0.00343

GnomAD4 exome AF: 0.00300 AC: 4381 AN: 1461550 Hom.: 14 Cov.: 36 AF XY: 0.00293 AC XY: 2133 AN XY: 727086

African (AFR) AF: 0.000418 AC: 14 AN: 33480

American (AMR) AF: 0.000693 AC: 31 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0209 AC: 547 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86258

European-Finnish (FIN) AF: 0.00213 AC: 113 AN: 53096

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5768

European-Non Finnish (NFE) AF: 0.00310 AC: 3452 AN: 1111998

Other (OTH) AF: 0.00334 AC: 202 AN: 60390

GnomAD4 genome AF: 0.00253 AC: 386 AN: 152302 Hom.: 0 Cov.: 31 AF XY: 0.00227 AC XY: 169 AN XY: 74488

African (AFR) AF: 0.000481 AC: 20 AN: 41572

American (AMR) AF: 0.000523 AC: 8 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 85 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00254 AC: 27 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00354 AC: 241 AN: 68022

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00350 Hom.: 7

Bravo AF: 0.00240

ESP6500AA AF: 0.000455 AC: 2

ESP6500EA AF: 0.00488 AC: 42

ExAC AF: 0.00287 AC: 349

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00349

EpiControl AF: 0.00356

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Severe combined immunodeficiency due to CORO1A deficiency (2)
-	-	1	CORO1A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.39
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		6.8
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.22
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.027	D
Polyphen		0.93	P
Vest4		0.34
MVP		0.30
MPC		1.9
ClinPred		0.043	T
GERP RS		5.8
Varity_R		0.13
gMVP		0.41
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs150857828; hg19: chr16-30199713; COSMIC: COSV106089945; COSMIC: COSV106089945;