rs73936843

Variant names:

• chr19-44672570-C-T
• rs73936843
• NM_001127893.3:c.56-26C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. 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 rank	MANE	Protein	UniProt
CEACAM19	NM_001127893.3	c.56-26C>T		intron_variant	Intron 1 of 7	ENST00000358777.10	NP_001121365.1
CEACAM19	NM_020219.5	c.56-26C>T		intron_variant	Intron 1 of 7		NP_064604.2
CEACAM19	NM_001389722.1	c.56-26C>T		intron_variant	Intron 2 of 8		NP_001376651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEACAM19	ENST00000358777.10	c.56-26C>T		intron_variant	Intron 1 of 7	1	NM_001127893.3	ENSP00000351627.4

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

GnomAD2 exomes AF: 0.0228 AC: 3330 AN: 146092 AF XY: 0.0193

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 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

African (AFR) AF: 0.137 AC: 3861 AN: 28102

American (AMR) AF: 0.0116 AC: 265 AN: 22856

Ashkenazi Jewish (ASJ) AF: 0.0129 AC: 244 AN: 18926

East Asian (EAS) AF: 0.0439 AC: 1533 AN: 34934

South Asian (SAS) AF: 0.0400 AC: 2380 AN: 59426

European-Finnish (FIN) AF: 0.0341 AC: 1667 AN: 48936

Middle Eastern (MID) AF: 0.0105 AC: 38 AN: 3628

European-Non Finnish (NFE) AF: 0.000468 AC: 486 AN: 1037452

Other (OTH) AF: 0.0155 AC: 827 AN: 53476

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

African (AFR) AF: 0.129 AC: 5348 AN: 41496

American (AMR) AF: 0.0229 AC: 350 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 36 AN: 3472

East Asian (EAS) AF: 0.0230 AC: 119 AN: 5168

South Asian (SAS) AF: 0.0369 AC: 178 AN: 4822

European-Finnish (FIN) AF: 0.0336 AC: 357 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00146 AC: 99 AN: 68020

Other (OTH) AF: 0.0318 AC: 67 AN: 2110

Alfa AF: 0.0251 Hom.: 62

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
PhyloP100		1.6
BranchPoint Hunter		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs73936843; hg19: chr19-45175842; COSMIC: COSV62552157;