Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_007074.4(CORO1A):c.1078delC(p.Gln360ArgfsTer45) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000205 in 1,461,588 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Q360Q) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CORO1A
NM_007074.4 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 4.11

Publications

3 publications found

Variant links:

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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics
epidermodysplasia verruciformis
Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
autism spectrum disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

CORO1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 12 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 16-30188371-TC-T is Pathogenic according to our data. Variant chr16-30188371-TC-T is described in ClinVar as Pathogenic. ClinVar VariationId is 157509.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORO1A	NM_007074.4	MANE Select	c.1078delC	p.Gln360ArgfsTer45	frameshift	Exon 10 of 11	NP_009005.1
	CORO1A	NM_001193333.3		c.1078delC	p.Gln360ArgfsTer45	frameshift	Exon 11 of 12	NP_001180262.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CORO1A	ENST00000219150.10	TSL:1 MANE Select	c.1078delC	p.Gln360ArgfsTer45	frameshift	Exon 10 of 11	ENSP00000219150.6
CORO1A	ENST00000570045.5	TSL:1	c.1078delC	p.Gln360ArgfsTer45	frameshift	Exon 11 of 12	ENSP00000455552.1
CORO1A	ENST00000562129.1	TSL:2	n.188delC		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461588

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727104

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53136

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111998

Other (OTH)

AF:

0.0000166

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Severe combined immunodeficiency due to CORO1A deficiency (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.1

Mutation Taster

=3/197

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.29

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.29

Position offset: 30

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs606231256

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over