chr19-41797757-T-A

Variant names:

• chr19-41797757-T-A
• rs61738269
• NM_001815.5:c.233T>A

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.233T>A​(p.Leu78Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0074 in 1,603,950 control chromosomes in the GnomAD database, including 1,100 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 0.043 (512 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (588 hom.)
• Consequence: CEACAM3 NM_001815.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.97
• 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=0.0046284795).
• BP6: Variant 19-41797757-T-A is Benign according to our data. Variant chr19-41797757-T-A is described in ClinVar as Benign. ClinVar VariationId is 769004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 512 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.233T>A	p.Leu78Gln	missense	Exon 2 of 7	NP_001806.2	P40198-1
	CEACAM3	NM_001277163.3		c.233T>A	p.Leu78Gln	missense	Exon 2 of 6	NP_001264092.1	P40198-3
	CEACAM3	NR_102333.3		n.324T>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.233T>A	p.Leu78Gln	missense	Exon 2 of 7	ENSP00000349971.3	P40198-1
	CEACAM3	ENST00000344550.4	TSL:1	c.233T>A	p.Leu78Gln	missense	Exon 2 of 6	ENSP00000341725.4	P40198-3
	CEACAM3	ENST00000415495.5	TSL:1	n.233T>A		non_coding_transcript_exon	Exon 2 of 8	ENSP00000411641.1	P40198-2

Frequencies

GnomAD3 genomes AF: 0.0430 AC: 6400 AN: 148928 Hom.: 495 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.0319

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000574

Gnomad OTH AF: 0.0335

GnomAD2 exomes AF: 0.00557 AC: 1382 AN: 247962 AF XY: 0.00446

Gnomad AFR exome AF: 0.0851

Gnomad AMR exome AF: 0.00361

Gnomad ASJ exome AF: 0.00629

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000220

Gnomad OTH exome AF: 0.00214

GnomAD4 exome AF: 0.00373 AC: 5426 AN: 1454916 Hom.: 588 Cov.: 31 AF XY: 0.00331 AC XY: 2400 AN XY: 724342

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

African (AFR) AF: 0.127 AC: 3655 AN: 28806

American (AMR) AF: 0.00703 AC: 312 AN: 44400

Ashkenazi Jewish (ASJ) AF: 0.0217 AC: 552 AN: 25470

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

South Asian (SAS) AF: 0.000383 AC: 33 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00523 AC: 30 AN: 5734

European-Non Finnish (NFE) AF: 0.000237 AC: 263 AN: 1111410

Other (OTH) AF: 0.00972 AC: 581 AN: 59748

⚠️ 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: 0.0432 AC: 6444 AN: 149034 Hom.: 512 Cov.: 32 AF XY: 0.0418 AC XY: 3045 AN XY: 72848

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

African (AFR) AF: 0.155 AC: 5999 AN: 38776

American (AMR) AF: 0.0146 AC: 220 AN: 15120

Ashkenazi Jewish (ASJ) AF: 0.0319 AC: 109 AN: 3418

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.00146 AC: 7 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

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

European-Non Finnish (NFE) AF: 0.000574 AC: 39 AN: 67918

Other (OTH) AF: 0.0332 AC: 69 AN: 2080

⚠️ 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: 0.0159 Hom.: 70

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0130 AC: 1574

EpiCase AF: 0.00109

EpiControl AF: 0.000594

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	0.088
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.010
DANN	Benign	0.21
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.17	T
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.67	N
PhyloP100		-2.0
PrimateAI	Benign	0.26	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.072
Sift	Benign	0.37	T
Sift4G	Benign	0.38	T
Polyphen		0.28	B
Vest4		0.067
MPC		0.17
ClinPred		0.0024	T
GERP RS		-2.6
Varity_R		0.18
gMVP		0.27
Mutation Taster		=99/1	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: rs61738269; hg19: chr19-42301689;