16-30186830-A-G

Position:

chr16-30186830-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_007074.4(CORO1A):c.336A>G(p.Pro112Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 1,610,452 control chromosomes in the GnomAD database, including 281,087 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 36953 hom., cov: 33)

Exomes 𝑓: 0.57 ( 244134 hom. )

Consequence

CORO1A
NM_007074.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: -6.22

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 links:

CORO1A (HGNC:):

CORO1A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 16-30186830-A-G is Benign according to our data. Variant chr16-30186830-A-G is described in ClinVar as [Benign]. Clinvar id is 379386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-30186830-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-6.22 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CORO1A	NM_007074.4 linkuse as main transcript	c.336A>G	p.Pro112Pro	synonymous_variant	4/11	ENST00000219150.10	NP_009005.1	P31146A0A024R611
CORO1A	NM_001193333.3 linkuse as main transcript	c.336A>G	p.Pro112Pro	synonymous_variant	5/12		NP_001180262.1	P31146A0A024R611

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CORO1A	ENST00000219150.10 linkuse as main transcript	c.336A>G	p.Pro112Pro	synonymous_variant	4/11	1	NM_007074.4	ENSP00000219150.6		P31146

Frequencies

GnomAD3 genomes

AF:

0.677

AC:

102901

AN:

151998

Hom.:

36885

Cov.:

show subpopulations

Gnomad AFR

AF:

0.894

Gnomad AMI

AF:

0.463

Gnomad AMR

AF:

0.693

Gnomad ASJ

AF:

0.671

Gnomad EAS

AF:

0.930

Gnomad SAS

AF:

0.706

Gnomad FIN

AF:

0.617

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.534

Gnomad OTH

AF:

0.656

GnomAD3 exomes

AF:

0.654

AC:

161348

AN:

246798

Hom.:

55096

AF XY:

0.642

AC XY:

86218

AN XY:

134316

show subpopulations

Gnomad AFR exome

AF:

0.906

Gnomad AMR exome

AF:

0.772

Gnomad ASJ exome

AF:

0.660

Gnomad EAS exome

AF:

0.931

Gnomad SAS exome

AF:

0.680

Gnomad FIN exome

AF:

0.602

Gnomad NFE exome

AF:

0.540

Gnomad OTH exome

AF:

0.624

GnomAD4 exome

AF:

0.569

AC:

830073

AN:

1458336

Hom.:

244134

Cov.:

AF XY:

0.571

AC XY:

414203

AN XY:

725694

show subpopulations

Gnomad4 AFR exome

AF:

0.909

Gnomad4 AMR exome

AF:

0.760

Gnomad4 ASJ exome

AF:

0.657

Gnomad4 EAS exome

AF:

0.903

Gnomad4 SAS exome

AF:

0.680

Gnomad4 FIN exome

AF:

0.609

Gnomad4 NFE exome

AF:

0.525

Gnomad4 OTH exome

AF:

0.605

GnomAD4 genome

AF:

0.677

AC:

103032

AN:

152116

Hom.:

36953

Cov.:

AF XY:

0.683

AC XY:

50772

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.894

Gnomad4 AMR

AF:

0.693

Gnomad4 ASJ

AF:

0.671

Gnomad4 EAS

AF:

0.930

Gnomad4 SAS

AF:

0.706

Gnomad4 FIN

AF:

0.617

Gnomad4 NFE

AF:

0.534

Gnomad4 OTH

AF:

0.661

Alfa

AF:

0.556

Hom.:

23202

Bravo

AF:

0.699

Asia WGS

AF:

0.835

AC:

2901

AN:

3478

EpiCase

AF:

0.556

EpiControl

AF:

0.552

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 83% of patients studied by a panel of primary immunodeficiencies. Number of patients: 80. Only high quality variants are reported. -
Benign, flagged submission	clinical testing	GeneDx	Oct 20, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:2Other:1

not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 05, 2022	- -

Severe combined immunodeficiency due to CORO1A deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.095

DANN

Benign

0.58

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over