NM_007074.4:c.336A>G

Variant names:

• chr16-30186830-A-G
• rs1132812
• NM_007074.4:c.336A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7 O:1
• Conservation: PhyloP100: -6.22
• Publications: 39 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 -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 VariationId is 379386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

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.336A>G	p.Pro112Pro	synonymous	Exon 4 of 11	NP_009005.1
	CORO1A	NM_001193333.3		c.336A>G	p.Pro112Pro	synonymous	Exon 5 of 12	NP_001180262.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORO1A	ENST00000219150.10	TSL:1 MANE Select	c.336A>G	p.Pro112Pro	synonymous	Exon 4 of 11	ENSP00000219150.6
	CORO1A	ENST00000570045.5	TSL:1	c.336A>G	p.Pro112Pro	synonymous	Exon 5 of 12	ENSP00000455552.1
	CORO1A	ENST00000891502.1		c.336A>G	p.Pro112Pro	synonymous	Exon 5 of 12	ENSP00000561561.1

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102901 AN: 151998 Hom.: 36885 Cov.: 33

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

GnomAD2 exomes AF: 0.654 AC: 161348 AN: 246798 AF XY: 0.642

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 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.: 63 AF XY: 0.571 AC XY: 414203 AN XY: 725694

African (AFR) AF: 0.909 AC: 30429 AN: 33476

American (AMR) AF: 0.760 AC: 33968 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 17174 AN: 26132

East Asian (EAS) AF: 0.903 AC: 35854 AN: 39696

South Asian (SAS) AF: 0.680 AC: 58661 AN: 86244

European-Finnish (FIN) AF: 0.609 AC: 30496 AN: 50086

Middle Eastern (MID) AF: 0.633 AC: 3631 AN: 5740

European-Non Finnish (NFE) AF: 0.525 AC: 583323 AN: 1111890

Other (OTH) AF: 0.605 AC: 36537 AN: 60364

GnomAD4 genome AF: 0.677 AC: 103032 AN: 152116 Hom.: 36953 Cov.: 33 AF XY: 0.683 AC XY: 50772 AN XY: 74370

African (AFR) AF: 0.894 AC: 37123 AN: 41522

American (AMR) AF: 0.693 AC: 10595 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2327 AN: 3470

East Asian (EAS) AF: 0.930 AC: 4791 AN: 5154

South Asian (SAS) AF: 0.706 AC: 3406 AN: 4826

European-Finnish (FIN) AF: 0.617 AC: 6528 AN: 10586

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.534 AC: 36278 AN: 67958

Other (OTH) AF: 0.661 AC: 1395 AN: 2112

Alfa AF: 0.574 Hom.: 37861

Bravo AF: 0.699

Asia WGS AF: 0.835 AC: 2901 AN: 3478

EpiCase AF: 0.556

EpiControl AF: 0.552

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (3)
-	-	2	Severe combined immunodeficiency due to CORO1A deficiency (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.095
DANN	Benign	0.58
PhyloP100		-6.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs1132812; hg19: chr16-30198151; COSMIC: COSV54631480; COSMIC: COSV54631480;