chr19-44672570-C-T

Position:

• chr19-44672570-C-T

Variant summary

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

The NM_001127893.3(CEACAM19):​c.56-26C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,459,940 control chromosomes in the GnomAD database, including 823 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.043 (355 hom., cov: 32)
  • Exomes 𝑓: 0.0086 (468 hom.)
• Consequence: CEACAM19 NM_001127893.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: This place is a probable branch point but likely benign (scored 2 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEACAM19	NM_001127893.3	c.56-26C>T		intron_variant		ENST00000358777.10	NP_001121365.1
CEACAM19	NM_001389722.1	c.56-26C>T		intron_variant			NP_001376651.1
CEACAM19	NM_020219.5	c.56-26C>T		intron_variant			NP_064604.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEACAM19	ENST00000358777.10	c.56-26C>T		intron_variant		1	NM_001127893.3	ENSP00000351627	A2
CEACAM16-AS1	ENST00000662585.1	n.475+26514G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0430 AC: 6543 AN: 152086 Hom.: 355 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0229

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.0232

Gnomad SAS AF: 0.0373

Gnomad FIN AF: 0.0336

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00146

Gnomad OTH AF: 0.0321

GnomAD3 exomes AF: 0.0228 AC: 3330 AN: 146092 Hom.: 174 AF XY: 0.0193 AC XY: 1499 AN XY: 77646

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.0102

Gnomad ASJ exome AF: 0.0123

Gnomad EAS exome AF: 0.0134

Gnomad SAS exome AF: 0.0424

Gnomad FIN exome AF: 0.0366

Gnomad NFE exome AF: 0.00234

Gnomad OTH exome AF: 0.0134

GnomAD4 exome AF: 0.00864 AC: 11301 AN: 1307736 Hom.: 468 Cov.: 30 AF XY: 0.00908 AC XY: 5779 AN XY: 636306

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.0116

Gnomad4 ASJ exome AF: 0.0129

Gnomad4 EAS exome AF: 0.0439

Gnomad4 SAS exome AF: 0.0400

Gnomad4 FIN exome AF: 0.0341

Gnomad4 NFE exome AF: 0.000468

Gnomad4 OTH exome AF: 0.0155

GnomAD4 genome AF: 0.0431 AC: 6555 AN: 152204 Hom.: 355 Cov.: 32 AF XY: 0.0435 AC XY: 3239 AN XY: 74424

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.0229

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.0230

Gnomad4 SAS AF: 0.0369

Gnomad4 FIN AF: 0.0336

Gnomad4 NFE AF: 0.00146

Gnomad4 OTH AF: 0.0318

Alfa AF: 0.0245 Hom.: 28

Bravo AF: 0.0461

Asia WGS AF: 0.0360 AC: 127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.76
BranchPoint Hunter		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs73936843; hg19: chr19-45175842; COSMIC: COSV62552157;