rs2302188

Positions:

• chr19-41579520-G-A

Variant summary

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

The NM_001098506.4(CEACAM21):​c.592G>A​(p.Val198Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,612,658 control chromosomes in the GnomAD database, including 65,864 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.35 (11036 hom., cov: 31)
  • Exomes 𝑓: 0.27 (54828 hom.)
• Consequence: CEACAM21 NM_001098506.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270

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]

CEACAM21 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0048744977).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEACAM21	NM_001098506.4	c.592G>A	p.Val198Met	missense_variant	3/7	ENST00000401445.4	NP_001091976.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEACAM21	ENST00000401445.4	c.592G>A	p.Val198Met	missense_variant	3/7	1	NM_001098506.4	ENSP00000385739.2
CEACAM21	ENST00000457737.5	n.*99G>A		non_coding_transcript_exon_variant	3/7	1		ENSP00000390697.1
CEACAM21	ENST00000457737.5	n.*99G>A		3_prime_UTR_variant	3/7	1		ENSP00000390697.1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53468 AN: 151726 Hom.: 11011 Cov.: 31

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.324

GnomAD4 exome AF: 0.266 AC: 388848 AN: 1460814 Hom.: 54828 Cov.: 36 AF XY: 0.267 AC XY: 193919 AN XY: 726576

Gnomad4 AFR exome AF: 0.582

Gnomad4 AMR exome AF: 0.174

Gnomad4 ASJ exome AF: 0.293

Gnomad4 EAS exome AF: 0.434

Gnomad4 SAS exome AF: 0.295

Gnomad4 FIN exome AF: 0.324

Gnomad4 NFE exome AF: 0.248

Gnomad4 OTH exome AF: 0.289

GnomAD4 genome AF: 0.353 AC: 53536 AN: 151844 Hom.: 11036 Cov.: 31 AF XY: 0.353 AC XY: 26197 AN XY: 74196

Gnomad4 AFR AF: 0.571

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.324

Alfa AF: 0.271 Hom.: 15718

Bravo AF: 0.354

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
MetaRNN	Benign	0.0049	T;T;T
Sift4G	Benign	0.12	T;D;D
Vest4		0.057
gMVP		0.17

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2302188; hg19: chr19-42085873;