19-44517149-G-A

Position:

• chr19-44517149-G-A

Variant summary

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

The NM_001102597.3(CEACAM20):​c.1106C>T​(p.Ser369Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,613,276 control chromosomes in the GnomAD database, including 11,302 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/12 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 0.14 (2124 hom., cov: 31)
  • Exomes 𝑓: 0.099 (9178 hom.)
• Consequence: CEACAM20 NM_001102597.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005539626).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEACAM20	NM_001102597.3	c.1106C>T	p.Ser369Phe	missense_variant	6/12	ENST00000614924.5	NP_001096067.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEACAM20	ENST00000614924.5	c.1106C>T	p.Ser369Phe	missense_variant	6/12	1	NM_001102597.3	ENSP00000481937	A2

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21990 AN: 151918 Hom.: 2120 Cov.: 31

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0333

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0818

Gnomad OTH AF: 0.158

GnomAD3 exomes AF: 0.135 AC: 33566 AN: 248560 Hom.: 3064 AF XY: 0.129 AC XY: 17444 AN XY: 134834

Gnomad AFR exome AF: 0.249

Gnomad AMR exome AF: 0.279

Gnomad ASJ exome AF: 0.136

Gnomad EAS exome AF: 0.138

Gnomad SAS exome AF: 0.171

Gnomad FIN exome AF: 0.0371

Gnomad NFE exome AF: 0.0841

Gnomad OTH exome AF: 0.126

GnomAD4 exome AF: 0.0993 AC: 145074 AN: 1461240 Hom.: 9178 Cov.: 33 AF XY: 0.100 AC XY: 73044 AN XY: 726892

Gnomad4 AFR exome AF: 0.251

Gnomad4 AMR exome AF: 0.272

Gnomad4 ASJ exome AF: 0.135

Gnomad4 EAS exome AF: 0.138

Gnomad4 SAS exome AF: 0.168

Gnomad4 FIN exome AF: 0.0377

Gnomad4 NFE exome AF: 0.0816

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.145 AC: 22019 AN: 152036 Hom.: 2124 Cov.: 31 AF XY: 0.146 AC XY: 10814 AN XY: 74318

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.0333

Gnomad4 NFE AF: 0.0818

Gnomad4 OTH AF: 0.159

Alfa AF: 0.104 Hom.: 2198

Bravo AF: 0.165

TwinsUK AF: 0.0836 AC: 310

ALSPAC AF: 0.0885 AC: 341

ESP6500AA AF: 0.228 AC: 966

ESP6500EA AF: 0.0825 AC: 699

ExAC AF: 0.131 AC: 15806

Asia WGS AF: 0.203 AC: 705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Benign	0.78
DEOGEN2	Benign	0.17	.;T;.;.
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.81	T;T;T;T
MetaRNN	Benign	0.0055	T;T;T;T
PrimateAI	Benign	0.29	T
Sift4G	Uncertain	0.044	D;D;D;D
Polyphen		1.0	.;D;.;.
Vest4		0.12
GERP RS		2.4
Varity_R		0.11
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs10414398; hg19: chr19-45021210; COSMIC: COSV57601121;