rs117288362

Positions:

• chr16-30188258-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007074.4(CORO1A):​c.1065+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00321 in 1,613,566 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0039 (7 hom., cov: 31)
  • Exomes 𝑓: 0.0031 (137 hom.)
• Consequence: CORO1A NM_007074.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.586

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 16-30188258-C-T is Benign according to our data. Variant chr16-30188258-C-T is described in ClinVar as [Benign]. Clinvar id is 474495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CORO1A	NM_007074.4	c.1065+9C>T		intron_variant		ENST00000219150.10
CORO1A	NM_001193333.3	c.1065+9C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CORO1A	ENST00000219150.10	c.1065+9C>T		intron_variant		1	NM_007074.4	P1

Frequencies

GnomAD3 genomes AF: 0.00389 AC: 592 AN: 152172 Hom.: 7 Cov.: 31

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.0609

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.0174

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000809

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00626 AC: 1572 AN: 251212 Hom.: 36 AF XY: 0.00598 AC XY: 813 AN XY: 135866

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000173

Gnomad ASJ exome AF: 0.00139

Gnomad EAS exome AF: 0.0539

Gnomad SAS exome AF: 0.00163

Gnomad FIN exome AF: 0.0135

Gnomad NFE exome AF: 0.00162

Gnomad OTH exome AF: 0.00570

GnomAD4 exome AF: 0.00314 AC: 4586 AN: 1461280 Hom.: 137 Cov.: 36 AF XY: 0.00320 AC XY: 2325 AN XY: 726972

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000246

Gnomad4 ASJ exome AF: 0.00115

Gnomad4 EAS exome AF: 0.0739

Gnomad4 SAS exome AF: 0.00151

Gnomad4 FIN exome AF: 0.0133

Gnomad4 NFE exome AF: 0.000505

Gnomad4 OTH exome AF: 0.00341

GnomAD4 genome AF: 0.00387 AC: 589 AN: 152286 Hom.: 7 Cov.: 31 AF XY: 0.00498 AC XY: 371 AN XY: 74460

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.0604

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.0174

Gnomad4 NFE AF: 0.000809

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00112 Hom.: 2

Bravo AF: 0.00294

Asia WGS AF: 0.0260 AC: 90 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Severe combined immunodeficiency due to CORO1A deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 26, 2024

- -

CORO1A-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 23, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.6
DANN	Benign	0.87

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: rs117288362; hg19: chr16-30199579; COSMIC: COSV54631865; COSMIC: COSV54631865;