chr19-41586462-A-T

Variant names:

• chr19-41586462-A-T
• rs3745936
• NM_001098506.4:c.*1-2A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 4P and 8B. PVS1_Strong BA1

The NM_001098506.4(CEACAM21):​c.*1-2A>T variant causes a splice acceptor, intron 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, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376
• Publications: 33 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.4319728 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 rank	MANE	Protein	UniProt
CEACAM21	NM_001098506.4	c.*1-2A>T		splice_acceptor_variant, intron_variant	Intron 6 of 6	ENST00000401445.4	NP_001091976.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEACAM21	ENST00000401445.4	c.*1-2A>T		splice_acceptor_variant, intron_variant	Intron 6 of 6	1	NM_001098506.4	ENSP00000385739.2
CEACAM21	ENST00000457737.5	n.*387-2A>T		splice_acceptor_variant, intron_variant	Intron 6 of 6	1		ENSP00000390697.1

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

African (AFR) AF: 0.436 AC: 5541 AN: 12696

American (AMR) AF: 0.155 AC: 6072 AN: 39246

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 3720 AN: 15338

East Asian (EAS) AF: 0.361 AC: 6933 AN: 19190

South Asian (SAS) AF: 0.275 AC: 18854 AN: 68538

European-Finnish (FIN) AF: 0.234 AC: 8414 AN: 35962

Middle Eastern (MID) AF: 0.222 AC: 755 AN: 3404

European-Non Finnish (NFE) AF: 0.182 AC: 47075 AN: 258976

Other (OTH) AF: 0.226 AC: 5225 AN: 23156

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

African (AFR) AF: 0.456 AC: 18918 AN: 41458

American (AMR) AF: 0.215 AC: 3283 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 943 AN: 3470

East Asian (EAS) AF: 0.395 AC: 2039 AN: 5168

South Asian (SAS) AF: 0.294 AC: 1415 AN: 4816

European-Finnish (FIN) AF: 0.264 AC: 2791 AN: 10584

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14439 AN: 67952

Other (OTH) AF: 0.282 AC: 593 AN: 2100

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
PhyloP100		0.38

Splicing

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

Other links and lift over

dbSNP: rs3745936; hg19: chr19-42092815;