chr19-41761449-G-A

Position:

• chr19-41761449-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_002483.7(CEACAM6):​c.625G>A​(p.Asp209Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000874 in 1,614,180 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00067 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00090 (2 hom.)
• Consequence: CEACAM6 NM_002483.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.47

Genes affected

CEACAM6 (HGNC:1818): (CEA cell adhesion molecule 6) This gene encodes a protein that belongs to the carcinoembryonic antigen (CEA) family whose members are glycosyl phosphatidyl inositol (GPI) anchored cell surface glycoproteins. Members of this family play a role in cell adhesion and are widely used as tumor markers in serum immunoassay determinations of carcinoma. This gene affects the sensitivity of tumor cells to adenovirus infection. The protein encoded by this gene acts as a receptor for adherent-invasive E. coli adhesion to the surface of ileal epithelial cells in patients with Crohn's disease. This gene is clustered with genes and pseudogenes of the cell adhesion molecules subgroup of the CEA family on chromosome 19. [provided by RefSeq, Apr 2014]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06867564).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEACAM6	NM_002483.7	c.625G>A	p.Asp209Asn	missense_variant	3/6	ENST00000199764.7
CEACAM6	XM_011526990.3	c.625G>A	p.Asp209Asn	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEACAM6	ENST00000199764.7	c.625G>A	p.Asp209Asn	missense_variant	3/6	1	NM_002483.7	P1
	ENST00000601409.1	n.384-3368C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.000670 AC: 102 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000970

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000871 AC: 219 AN: 251494 Hom.: 0 AF XY: 0.000846 AC XY: 115 AN XY: 135922

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.00476

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00231

Gnomad NFE exome AF: 0.000932

Gnomad OTH exome AF: 0.000814

GnomAD4 exome AF: 0.000895 AC: 1309 AN: 1461892 Hom.: 2 Cov.: 32 AF XY: 0.000857 AC XY: 623 AN XY: 727246

Gnomad4 AFR exome AF: 0.000119

Gnomad4 AMR exome AF: 0.000201

Gnomad4 ASJ exome AF: 0.00555

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00202

Gnomad4 NFE exome AF: 0.000897

Gnomad4 OTH exome AF: 0.000629

GnomAD4 genome AF: 0.000670 AC: 102 AN: 152288 Hom.: 0 Cov.: 32 AF XY: 0.000698 AC XY: 52 AN XY: 74466

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00151

Gnomad4 NFE AF: 0.000970

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00114 Hom.: 0

Bravo AF: 0.000623

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00163 AC: 14

ExAC AF: 0.000634 AC: 77

EpiCase AF: 0.00120

EpiControl AF: 0.00107

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2021

The c.625G>A (p.D209N) alteration is located in exon 3 (coding exon 3) of the CEACAM6 gene. This alteration results from a G to A substitution at nucleotide position 625, causing the aspartic acid (D) at amino acid position 209 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Uncertain	1.0
Eigen	Benign	0.13
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.37	N
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.11
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.0030	D
Vest4		0.71
MVP		0.38
MPC		0.65
ClinPred		0.16	T
GERP RS		2.0
gMVP		0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs143709500; hg19: chr19-42265357; COSMIC: COSV52267534; COSMIC: COSV52267534;