19-44672666-G-T

Variant names:

• chr19-44672666-G-T
• rs767736727
• NM_001127893.3:c.126G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001127893.3(CEACAM19):​c.126G>T​(p.Gln42His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,384,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CEACAM19 NM_001127893.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.481
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036390334).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127893.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM19	NM_001127893.3	MANE Select	c.126G>T	p.Gln42His	missense	Exon 2 of 8	NP_001121365.1	Q7Z692-3
	CEACAM19	NM_020219.5		c.126G>T	p.Gln42His	missense	Exon 2 of 8	NP_064604.2
	CEACAM19	NM_001389722.1		c.126G>T	p.Gln42His	missense	Exon 3 of 9	NP_001376651.1	Q7Z692-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM19	ENST00000358777.10	TSL:1 MANE Select	c.126G>T	p.Gln42His	missense	Exon 2 of 8	ENSP00000351627.4	Q7Z692-3
	CEACAM19	ENST00000403660.3	TSL:1	c.126G>T	p.Gln42His	missense	Exon 2 of 8	ENSP00000384887.3	Q7Z692-1
	CEACAM19	ENST00000911248.1		c.126G>T	p.Gln42His	missense	Exon 3 of 10	ENSP00000581307.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000102 AC: 2 AN: 195570 AF XY: 0.0000191

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000660

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1384054 Hom.: 0 Cov.: 31 AF XY: 0.00000147 AC XY: 1 AN XY: 681872

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30772

American (AMR) AF: 0.00 AC: 0 AN: 33866

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22186

East Asian (EAS) AF: 0.00 AC: 0 AN: 37056

South Asian (SAS) AF: 0.0000135 AC: 1 AN: 74012

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51538

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5434

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1072242

Other (OTH) AF: 0.00 AC: 0 AN: 56948

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000825 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.7
DANN	Benign	0.89
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.025	N
PhyloP100		-0.48
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.077
Sift	Benign	0.34	T
Sift4G	Benign	0.41	T
Polyphen		0.0020	B
Vest4		0.16
MutPred		0.28		Loss of methylation at K45 (P = 0.0666)
MVP		0.11
MPC		0.10
ClinPred		0.015	T
GERP RS		-1.2
Varity_R		0.046
gMVP		0.28
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs767736727; hg19: chr19-45175938;