NM_001815.5:c.229A>C

Variant names:

• chr19-41797753-A-C
• rs61738270
• NM_001815.5:c.229A>C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001815.5(CEACAM3):​c.229A>C​(p.Ser77Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00807 in 1,605,928 control chromosomes in the GnomAD database, including 1,143 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (526 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (617 hom.)
• Consequence: CEACAM3 NM_001815.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.36
• Publications: 4 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

ENSG00000268833 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0025494099).
• BP6: Variant 19-41797753-A-C is Benign according to our data. Variant chr19-41797753-A-C is described in ClinVar as Benign. ClinVar VariationId is 769003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 526 AR gene

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.229A>C	p.Ser77Arg	missense	Exon 2 of 7	NP_001806.2	P40198-1
	CEACAM3	NM_001277163.3		c.229A>C	p.Ser77Arg	missense	Exon 2 of 6	NP_001264092.1	P40198-3
	CEACAM3	NR_102333.3		n.320A>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.229A>C	p.Ser77Arg	missense	Exon 2 of 7	ENSP00000349971.3	P40198-1
	CEACAM3	ENST00000344550.4	TSL:1	c.229A>C	p.Ser77Arg	missense	Exon 2 of 6	ENSP00000341725.4	P40198-3
	CEACAM3	ENST00000415495.5	TSL:1	n.229A>C		non_coding_transcript_exon	Exon 2 of 8	ENSP00000411641.1	P40198-2

Frequencies

GnomAD3 genomes AF: 0.0443 AC: 6620 AN: 149476 Hom.: 508 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0155

Gnomad ASJ AF: 0.0338

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.0354

GnomAD2 exomes AF: 0.00611 AC: 1514 AN: 247642 AF XY: 0.00481

Gnomad AFR exome AF: 0.0948

Gnomad AMR exome AF: 0.00376

Gnomad ASJ exome AF: 0.00796

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000238

Gnomad OTH exome AF: 0.00214

GnomAD4 exome AF: 0.00433 AC: 6299 AN: 1456344 Hom.: 617 Cov.: 31 AF XY: 0.00381 AC XY: 2765 AN XY: 724936

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

African (AFR) AF: 0.143 AC: 4281 AN: 29860

American (AMR) AF: 0.00761 AC: 338 AN: 44424

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 625 AN: 25556

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

South Asian (SAS) AF: 0.000406 AC: 35 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00627 AC: 36 AN: 5744

European-Non Finnish (NFE) AF: 0.000301 AC: 335 AN: 1111538

Other (OTH) AF: 0.0108 AC: 649 AN: 59868

⚠️ 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: 0.0446 AC: 6667 AN: 149584 Hom.: 526 Cov.: 32 AF XY: 0.0435 AC XY: 3181 AN XY: 73198

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

African (AFR) AF: 0.158 AC: 6196 AN: 39190

American (AMR) AF: 0.0153 AC: 232 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.0338 AC: 116 AN: 3432

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.000603 AC: 41 AN: 67940

Other (OTH) AF: 0.0350 AC: 73 AN: 2086

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0146 Hom.: 71

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0132 AC: 1606

EpiCase AF: 0.00115

EpiControl AF: 0.000654

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
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.0050
DANN	Benign	0.16
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.00076	N
LIST_S2	Benign	0.028	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.2	N
PhyloP100		-1.4
PrimateAI	Benign	0.23	T
PROVEAN	Benign	2.6	N
REVEL	Benign	0.044
Sift	Benign	0.74	T
Sift4G	Benign	0.50	T
Polyphen		0.0	B
Vest4		0.071
MutPred		0.24		Loss of glycosylation at S77 (P = 0.0901)
MPC		0.11
ClinPred		0.0018	T
GERP RS		-6.9
Varity_R		0.066
gMVP		0.20
Mutation Taster		=99/1	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: rs61738270; hg19: chr19-42301685;