chr19-41797929-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001815.5(CEACAM3):​c.405T>A​(p.Thr135Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T135T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CEACAM3 NM_001815.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=0.127 with no splicing effect.

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>A	p.Thr135Thr	synonymous	Exon 2 of 7	NP_001806.2	P40198-1
	CEACAM3	NM_001277163.3		c.405T>A	p.Thr135Thr	synonymous	Exon 2 of 6	NP_001264092.1	P40198-3
	CEACAM3	NR_102333.3		n.496T>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.405T>A	p.Thr135Thr	synonymous	Exon 2 of 7	ENSP00000349971.3	P40198-1
	CEACAM3	ENST00000344550.4	TSL:1	c.405T>A	p.Thr135Thr	synonymous	Exon 2 of 6	ENSP00000341725.4	P40198-3
	CEACAM3	ENST00000415495.5	TSL:1	n.405T>A		non_coding_transcript_exon	Exon 2 of 8	ENSP00000411641.1	P40198-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455854 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724096

African (AFR) AF: 0.00 AC: 0 AN: 33220

American (AMR) AF: 0.00 AC: 0 AN: 44392

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 85404

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53008

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108860

Other (OTH) AF: 0.00 AC: 0 AN: 60108

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.84
DANN	Benign	0.39
PhyloP100		0.13

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;