19-41797833-C-A

Variant names:

• chr19-41797833-C-A
• rs61736644
• NM_001815.5:c.309C>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001815.5(CEACAM3):​c.309C>A​(p.Thr103Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00505 in 1,613,112 control chromosomes in the GnomAD database, including 412 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (244 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (168 hom.)
• Consequence: CEACAM3 NM_001815.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.279
• Publications: 0 publications found

Genes affected

CEACAM3 (HGNC:1815): (CEA cell adhesion molecule 3) This gene encodes a member of the family of carcinoembryonic antigen-related cell adhesion molecules (CEACAMs), which are used by several bacterial pathogens to bind and invade host cells. The encoded transmembrane protein directs phagocytosis of several bacterial species that is dependent on the small GTPase Rac. It is thought to serve an important role in controlling human-specific pathogens by the innate immune system. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2013]

CEACAM3 Gene-Disease associations (from GenCC):

• cystic fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 19-41797833-C-A is Benign according to our data. Variant chr19-41797833-C-A is described in ClinVar as Benign. ClinVar VariationId is 777493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.279 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0894 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001815.5. 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
	CEACAM3	NM_001815.5	MANE Select	c.309C>A	p.Thr103Thr	synonymous	Exon 2 of 7	NP_001806.2	P40198-1
	CEACAM3	NM_001277163.3		c.309C>A	p.Thr103Thr	synonymous	Exon 2 of 6	NP_001264092.1	P40198-3
	CEACAM3	NR_102333.3		n.400C>A		non_coding_transcript_exon	Exon 2 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM3	ENST00000357396.8	TSL:1 MANE Select	c.309C>A	p.Thr103Thr	synonymous	Exon 2 of 7	ENSP00000349971.3	P40198-1
	CEACAM3	ENST00000344550.4	TSL:1	c.309C>A	p.Thr103Thr	synonymous	Exon 2 of 6	ENSP00000341725.4	P40198-3
	CEACAM3	ENST00000415495.5	TSL:1	n.309C>A		non_coding_transcript_exon	Exon 2 of 8	ENSP00000411641.1	P40198-2

Frequencies

GnomAD3 genomes AF: 0.0260 AC: 3935 AN: 151210 Hom.: 244 Cov.: 32

Gnomad AFR AF: 0.0919

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00872

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.0168

GnomAD2 exomes AF: 0.00755 AC: 1899 AN: 251364 AF XY: 0.00562

Gnomad AFR exome AF: 0.0986

Gnomad AMR exome AF: 0.00523

Gnomad ASJ exome AF: 0.00318

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000466

Gnomad OTH exome AF: 0.00505

GnomAD4 exome AF: 0.00288 AC: 4203 AN: 1461784 Hom.: 168 Cov.: 31 AF XY: 0.00252 AC XY: 1832 AN XY: 727192

African (AFR) AF: 0.0924 AC: 3084 AN: 33394

American (AMR) AF: 0.00584 AC: 261 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00329 AC: 86 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00763 AC: 44 AN: 5766

European-Non Finnish (NFE) AF: 0.000266 AC: 296 AN: 1112006

Other (OTH) AF: 0.00682 AC: 412 AN: 60392

GnomAD4 genome AF: 0.0261 AC: 3945 AN: 151328 Hom.: 244 Cov.: 32 AF XY: 0.0253 AC XY: 1872 AN XY: 73978

African (AFR) AF: 0.0918 AC: 3730 AN: 40622

American (AMR) AF: 0.00871 AC: 133 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.000529 AC: 36 AN: 68018

Other (OTH) AF: 0.0166 AC: 35 AN: 2106

Alfa AF: 0.00732 Hom.: 14

Bravo AF: 0.0293

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000711

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.2
DANN	Benign	0.36
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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: rs61736644; hg19: chr19-42301765;