NM_007074.4:c.1065+9C>T

Variant names:

• chr16-30188258-C-T
• rs117288362
• NM_007074.4:c.1065+9C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:2
• Conservation: PhyloP100: 0.586
• Publications: 1 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: 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

ACMG classification

Our verdict: Benign. The variant received -14 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 VariationId is 474495.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0549 is higher than 0.05.

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.1065+9C>T		intron	N/A	NP_009005.1
	CORO1A	NM_001193333.3		c.1065+9C>T		intron	N/A	NP_001180262.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORO1A	ENST00000219150.10	TSL:1 MANE Select	c.1065+9C>T		intron	N/A	ENSP00000219150.6
	CORO1A	ENST00000570045.5	TSL:1	c.1065+9C>T		intron	N/A	ENSP00000455552.1
	CORO1A	ENST00000891502.1		c.1065+9C>T		intron	N/A	ENSP00000561561.1

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

GnomAD2 exomes AF: 0.00626 AC: 1572 AN: 251212 AF XY: 0.00598

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 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

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.000246 AC: 11 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 30 AN: 26128

East Asian (EAS) AF: 0.0739 AC: 2935 AN: 39698

South Asian (SAS) AF: 0.00151 AC: 130 AN: 86248

European-Finnish (FIN) AF: 0.0133 AC: 711 AN: 53282

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.000505 AC: 561 AN: 1111580

Other (OTH) AF: 0.00341 AC: 206 AN: 60388

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

African (AFR) AF: 0.0000722 AC: 3 AN: 41568

American (AMR) AF: 0.000131 AC: 2 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.0604 AC: 312 AN: 5164

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4824

European-Finnish (FIN) AF: 0.0174 AC: 185 AN: 10616

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

European-Non Finnish (NFE) AF: 0.000809 AC: 55 AN: 68018

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00104 Hom.: 2

Bravo AF: 0.00294

Asia WGS AF: 0.0260 AC: 90 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	CORO1A-related disorder (1)
-	-	1	Severe combined immunodeficiency due to CORO1A deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.6
DANN	Benign	0.87
PhyloP100		0.59
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

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