chr19-41797929-T-C

Variant names:

• chr19-41797929-T-C
• rs61736640
• NM_001815.5:c.405T>C

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.405T>C​(p.Thr135Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00469 in 1,607,474 control chromosomes in the GnomAD database, including 323 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (192 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (131 hom.)
• Consequence: CEACAM3 NM_001815.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.127
• Publications: 1 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=-0.96).
• BP6: Variant 19-41797929-T-C is Benign according to our data. Variant chr19-41797929-T-C is described in ClinVar as Benign. ClinVar VariationId is 769009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.127 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0896 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.405T>C	p.Thr135Thr	synonymous	Exon 2 of 7	NP_001806.2	P40198-1
	CEACAM3	NM_001277163.3		c.405T>C	p.Thr135Thr	synonymous	Exon 2 of 6	NP_001264092.1	P40198-3
	CEACAM3	NR_102333.3		n.496T>C		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.405T>C	p.Thr135Thr	synonymous	Exon 2 of 7	ENSP00000349971.3	P40198-1
	CEACAM3	ENST00000344550.4	TSL:1	c.405T>C	p.Thr135Thr	synonymous	Exon 2 of 6	ENSP00000341725.4	P40198-3
	CEACAM3	ENST00000415495.5	TSL:1	n.405T>C		non_coding_transcript_exon	Exon 2 of 8	ENSP00000411641.1	P40198-2

Frequencies

GnomAD3 genomes AF: 0.0259 AC: 3944 AN: 152130 Hom.: 181 Cov.: 32

Gnomad AFR AF: 0.0913

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00733

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.0163

GnomAD2 exomes AF: 0.00680 AC: 1667 AN: 244970 AF XY: 0.00488

Gnomad AFR exome AF: 0.0897

Gnomad AMR exome AF: 0.00494

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000478

Gnomad NFE exome AF: 0.000335

Gnomad OTH exome AF: 0.00251

GnomAD4 exome AF: 0.00244 AC: 3550 AN: 1455226 Hom.: 131 Cov.: 31 AF XY: 0.00215 AC XY: 1557 AN XY: 723858

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

African (AFR) AF: 0.0820 AC: 2683 AN: 32712

American (AMR) AF: 0.00541 AC: 240 AN: 44384

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25440

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39686

South Asian (SAS) AF: 0.000246 AC: 21 AN: 85404

European-Finnish (FIN) AF: 0.0000566 AC: 3 AN: 53008

Middle Eastern (MID) AF: 0.00349 AC: 20 AN: 5732

European-Non Finnish (NFE) AF: 0.000192 AC: 213 AN: 1108788

Other (OTH) AF: 0.00613 AC: 368 AN: 60072

⚠️ 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 AF: 0.0262 AC: 3985 AN: 152248 Hom.: 192 Cov.: 32 AF XY: 0.0254 AC XY: 1890 AN XY: 74464

African (AFR) AF: 0.0920 AC: 3818 AN: 41506

American (AMR) AF: 0.00732 AC: 112 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68022

Other (OTH) AF: 0.0161 AC: 34 AN: 2112

Alfa AF: 0.00967 Hom.: 27

Bravo AF: 0.0301

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	-0.96
CADD	Benign	1.0
DANN	Benign	0.41
PhyloP100		0.13
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: rs61736640; hg19: chr19-42301861;