Variant 19-44680331-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001127893.3(CEACAM19):c.703G>T(p.Ala235Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000423 in 1,608,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00044 ( 0 hom. )

Consequence

CEACAM19
NM_001127893.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.89

Variant links:

Genes affected

CEACAM19 (HGNC:31951): (CEA cell adhesion molecule 19) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

CEACAM19 links:

CEACAM16-AS1 (HGNC:55317): (CEACAM16, CEACAM19 and PVR antisense RNA 1)

CEACAM16-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020131916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CEACAM19	NM_001127893.3 linkuse as main transcript	c.703G>T	p.Ala235Ser	missense_variant	5/8	ENST00000358777.10
CEACAM19	NM_020219.5 linkuse as main transcript	c.703G>T	p.Ala235Ser	missense_variant	5/8
CEACAM19	NM_001389722.1 linkuse as main transcript	c.703G>T	p.Ala235Ser	missense_variant	6/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEACAM19	ENST00000358777.10 linkuse as main transcript	c.703G>T	p.Ala235Ser	missense_variant	5/8	1	NM_001127893.3	A2	Q7Z692-3
CEACAM16-AS1	ENST00000662585.1 linkuse as main transcript	n.475+18753C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000266

AC:

AN:

150416

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000669

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000472

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000264

AC:

AN:

249984

Hom.:

AF XY:

0.000274

AC XY:

AN XY:

135134

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000537

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000440

AC:

641

AN:

1458344

Hom.:

Cov.:

AF XY:

0.000438

AC XY:

318

AN XY:

725542

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000586

Gnomad4 NFE exome

AF:

0.000546

Gnomad4 OTH exome

AF:

0.000431

GnomAD4 genome

AF:

0.000266

AC:

AN:

150534

Hom.:

Cov.:

AF XY:

0.000191

AC XY:

AN XY:

73440

show subpopulations

Gnomad4 AFR

AF:

0.000171

Gnomad4 AMR

AF:

0.0000668

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000472

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000412

Hom.:

Bravo

AF:

0.000227

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000173

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000383

EpiControl

AF:

0.000534

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 11, 2022

The c.703G>T (p.A235S) alteration is located in exon 5 (coding exon 5) of the CEACAM19 gene. This alteration results from a G to T substitution at nucleotide position 703, causing the alanine (A) at amino acid position 235 to be replaced by a serine (S). 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

Benign

0.081

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.0070

DANN

Benign

0.48

DEOGEN2

Benign

0.0023

.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0049

LIST_S2

Benign

0.31

T;T

M_CAP

Benign

0.0010

MetaRNN

Benign

0.020

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.38

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.090

N;N

REVEL

Benign

0.0080

Sift

Benign

0.39

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0040

.;B

Vest4

0.086

MVP

0.16

MPC

0.10

ClinPred

0.014

GERP RS

-5.0

Varity_R

0.045

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over