rs872375

Positions:

• chr11-67438507-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020441.3(CORO1B):​c.1345-6C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,603,860 control chromosomes in the GnomAD database, including 136,491 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.38 (11076 hom., cov: 35)
  • Exomes 𝑓: 0.41 (125415 hom.)
• Consequence: CORO1B NM_020441.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001010
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359

Genes affected

CORO1B (HGNC:2253): (coronin 1B) Members of the coronin family, such as CORO1B, are WD repeat-containing actin-binding proteins that regulate cell motility (Cai et al., 2005 [PubMed 16027158]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CORO1B	NM_020441.3	c.1345-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000341356.10
CORO1B	NM_001018070.3	c.1345-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CORO1B	ENST00000341356.10	c.1345-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_020441.3	P1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57264 AN: 152130 Hom.: 11064 Cov.: 35

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.369

GnomAD3 exomes AF: 0.391 AC: 92911 AN: 237730 Hom.: 19304 AF XY: 0.381 AC XY: 49480 AN XY: 129750

Gnomad AFR exome AF: 0.317

Gnomad AMR exome AF: 0.563

Gnomad ASJ exome AF: 0.315

Gnomad EAS exome AF: 0.286

Gnomad SAS exome AF: 0.260

Gnomad FIN exome AF: 0.353

Gnomad NFE exome AF: 0.416

Gnomad OTH exome AF: 0.391

GnomAD4 exome AF: 0.411 AC: 596934 AN: 1451612 Hom.: 125415 Cov.: 52 AF XY: 0.405 AC XY: 292122 AN XY: 720520

Gnomad4 AFR exome AF: 0.321

Gnomad4 AMR exome AF: 0.551

Gnomad4 ASJ exome AF: 0.311

Gnomad4 EAS exome AF: 0.307

Gnomad4 SAS exome AF: 0.265

Gnomad4 FIN exome AF: 0.357

Gnomad4 NFE exome AF: 0.429

Gnomad4 OTH exome AF: 0.393

GnomAD4 genome AF: 0.376 AC: 57313 AN: 152248 Hom.: 11076 Cov.: 35 AF XY: 0.370 AC XY: 27556 AN XY: 74462

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.367

Alfa AF: 0.398 Hom.: 5273

Bravo AF: 0.388

Asia WGS AF: 0.324 AC: 1129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.2
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00010
dbscSNV1_RF	Benign	0.016
SpliceAI score (max)		0.020		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: rs872375; hg19: chr11-67205978; COSMIC: COSV57047449; COSMIC: COSV57047449;