chr19-44513250-C-T

Position:

• chr19-44513250-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000614924.5(CEACAM20):​c.1349G>A​(p.Gly450Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,652 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CEACAM20 ENST00000614924.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.26

Genes affected

CEACAM20 (HGNC:24879): (CEA cell adhesion molecule 20) Predicted to be involved in positive regulation of cytokine production. Predicted to act upstream of or within response to bacterium. Predicted to be located in apical plasma membrane and microvillus membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEACAM20	NM_001102597.3	c.1349G>A	p.Gly450Asp	missense_variant	7/12	ENST00000614924.5	NP_001096067.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEACAM20	ENST00000614924.5	c.1349G>A	p.Gly450Asp	missense_variant	7/12	1	NM_001102597.3	ENSP00000481937.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 249008 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135100

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461652 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727104

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2024

The c.1349G>A (p.G450D) alteration is located in exon 7 (coding exon 7) of the CEACAM20 gene. This alteration results from a G to A substitution at nucleotide position 1349, causing the glycine (G) at amino acid position 450 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	22
DANN	Benign	0.88
DEOGEN2	Benign	0.14	.;.;.;T;.;.
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.81	T;T;T;T;T;T
MetaRNN	Uncertain	0.58	D;D;D;D;D;D
PrimateAI	Benign	0.39	T
Sift4G	Uncertain	0.025	D;D;D;D;D;D
Polyphen		1.0	.;.;.;D;.;.
Vest4		0.61
MVP		0.36
GERP RS		5.0
Varity_R		0.11
gMVP		0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs890740554; hg19: chr19-45017309;