rs3745936

chr19-41586462-A-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 4P and 8B. PVS1_Strong BA1

The NM_001098506.4(CEACAM21):c.*1-2A>T variant causes a splice acceptor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 628,536 control chromosomes in the GnomAD database, including 20,339 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (7426 hom., cov: 32)
  • Exomes 𝑓: 0.22 (12913 hom.)
• Consequence: CEACAM21 NM_001098506.4 splice_acceptor
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376

Genes affected

CEACAM21 (HGNC:28834): (CEA cell adhesion molecule 21) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PVS1: Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.2154195 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEACAM21	NM_001098506.4	c.*1-2A>T		splice_acceptor_variant		ENST00000401445.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEACAM21	ENST00000401445.4	c.*1-2A>T		splice_acceptor_variant		1	NM_001098506.4	P2

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44620 AN: 151912 Hom.: 7418 Cov.: 32

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.282

GnomAD4 exome AF: 0.215 AC: 102589 AN: 476506 Hom.: 12913 Cov.: 4 AF XY: 0.220 AC XY: 58222 AN XY: 264796

Gnomad4 AFR exome AF: 0.436

Gnomad4 AMR exome AF: 0.155

Gnomad4 ASJ exome AF: 0.243

Gnomad4 EAS exome AF: 0.361

Gnomad4 SAS exome AF: 0.275

Gnomad4 FIN exome AF: 0.234

Gnomad4 NFE exome AF: 0.182

Gnomad4 OTH exome AF: 0.226

GnomAD4 genome AF: 0.294 AC: 44659 AN: 152030 Hom.: 7426 Cov.: 32 AF XY: 0.295 AC XY: 21932 AN XY: 74320

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.282

Alfa AF: 0.248 Hom.: 935

Bravo AF: 0.296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	18

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3745936; hg19: chr19-42092815;