Genetic Variant NM_007074.4:c.804C>T (chr16-30187772-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_007074.4(CORO1A):c.804C>T(p.Ser268Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000984 in 1,554,798 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00072 ( 7 hom. )

Consequence

CORO1A
NM_007074.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -6.84

Publications

4 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: 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

CORO1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 16-30187772-C-T is Benign according to our data. Variant chr16-30187772-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 381252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6.84 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00361 (521/144206) while in subpopulation AFR AF = 0.0102 (405/39626). AF 95% confidence interval is 0.0094. There are 2 homozygotes in GnomAd4. There are 246 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 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.804C>T	p.Ser268Ser	synonymous	Exon 7 of 11	NP_009005.1	P31146
	CORO1A	NM_001193333.3		c.804C>T	p.Ser268Ser	synonymous	Exon 8 of 12	NP_001180262.1	P31146

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CORO1A	ENST00000219150.10	TSL:1 MANE Select	c.804C>T	p.Ser268Ser	synonymous	Exon 7 of 11	ENSP00000219150.6	P31146
CORO1A	ENST00000570045.5	TSL:1	c.804C>T	p.Ser268Ser	synonymous	Exon 8 of 12	ENSP00000455552.1	P31146
CORO1A	ENST00000891502.1		c.804C>T	p.Ser268Ser	synonymous	Exon 8 of 12	ENSP00000561561.1

Frequencies

GnomAD3 genomes

AF:

0.00359

AC:

517

AN:

144060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00413

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00331

Gnomad NFE

AF:

0.000622

Gnomad OTH

AF:

0.00794

GnomAD2 exomes

AF:

0.00119

AC:

299

AN:

250320

AF XY:

0.000966

show subpopulations

Gnomad AFR exome

AF:

0.00761

Gnomad AMR exome

AF:

0.00205

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000753

Gnomad OTH exome

AF:

0.00311

GnomAD4 exome

AF:

0.000715

AC:

1009

AN:

1410592

Hom.:

Cov.:

AF XY:

0.000675

AC XY:

473

AN XY:

701226

show subpopulations

African (AFR)

AF:

0.00973

AC:

311

AN:

31954

American (AMR)

AF:

0.00288

AC:

124

AN:

43128

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24346

East Asian (EAS)

AF:

0.0000567

AC:

AN:

35248

South Asian (SAS)

AF:

0.0000583

AC:

AN:

85812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49038

Middle Eastern (MID)

AF:

0.00366

AC:

AN:

5468

European-Non Finnish (NFE)

AF:

0.000401

AC:

432

AN:

1078472

Other (OTH)

AF:

0.00201

AC:

115

AN:

57126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

118

178

237

296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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

AF:

0.00361

AC:

521

AN:

144206

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

246

AN XY:

69900

show subpopulations

African (AFR)

AF:

0.0102

AC:

405

AN:

39626

American (AMR)

AF:

0.00412

AC:

AN:

14070

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3378

East Asian (EAS)

AF:

0.00

AC:

AN:

4452

South Asian (SAS)

AF:

0.00

AC:

AN:

4372

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9142

Middle Eastern (MID)

AF:

0.00357

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.000622

AC:

AN:

65966

Other (OTH)

AF:

0.00785

AC:

AN:

2038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

101

126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00183

Hom.:

Bravo

AF:

0.00410

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.00107

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

CORO1A-related disorder (1)

not specified (1)

Severe combined immunodeficiency due to CORO1A deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

2.5

(source)

DANN

Benign

0.86

PhyloP100

-6.8

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over