19-41756789-G-A

Position:

• chr19-41756789-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002483.7(CEACAM6):​c.254G>A​(p.Gly85Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0047 in 1,613,966 control chromosomes in the GnomAD database, including 276 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (163 hom., cov: 31)
  • Exomes 𝑓: 0.0027 (113 hom.)
• Consequence: CEACAM6 NM_002483.7 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.07

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]

LOC112268252 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019599497).
• BP6: Variant 19-41756789-G-A is Benign according to our data. Variant chr19-41756789-G-A is described in ClinVar as [Benign]. Clinvar id is 782649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEACAM6	NM_002483.7	c.254G>A	p.Gly85Glu	missense_variant	2/6	ENST00000199764.7
LOC112268252	XR_002958447.2	n.1628C>T		non_coding_transcript_exon_variant	2/2
CEACAM6	XM_011526990.3	c.254G>A	p.Gly85Glu	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEACAM6	ENST00000199764.7	c.254G>A	p.Gly85Glu	missense_variant	2/6	1	NM_002483.7	P1

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3612 AN: 151962 Hom.: 160 Cov.: 31

Gnomad AFR AF: 0.0823

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00793

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.0182

GnomAD3 exomes AF: 0.00701 AC: 1764 AN: 251474 Hom.: 76 AF XY: 0.00512 AC XY: 696 AN XY: 135910

Gnomad AFR exome AF: 0.0893

Gnomad AMR exome AF: 0.00645

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000510

Gnomad OTH exome AF: 0.00440

GnomAD4 exome AF: 0.00270 AC: 3942 AN: 1461886 Hom.: 113 Cov.: 33 AF XY: 0.00236 AC XY: 1714 AN XY: 727246

Gnomad4 AFR exome AF: 0.0870

Gnomad4 AMR exome AF: 0.00635

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000339

Gnomad4 OTH exome AF: 0.00530

GnomAD4 genome AF: 0.0239 AC: 3638 AN: 152080 Hom.: 163 Cov.: 31 AF XY: 0.0227 AC XY: 1687 AN XY: 74364

Gnomad4 AFR AF: 0.0828

Gnomad4 AMR AF: 0.00792

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000647

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.00175 Hom.: 0

Bravo AF: 0.0278

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.0815 AC: 359

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.00856 AC: 1039

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 28, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.0030
DANN	Benign	0.25
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.5
FATHMM_MKL	Benign	0.00036	N
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.46	N
REVEL	Benign	0.099
Sift	Benign	0.12	T
Sift4G	Benign	0.39	T
Vest4		0.074
MVP		0.34
MPC		0.20
ClinPred		0.0049	T
GERP RS		-3.8
gMVP		0.32

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: rs61736638; hg19: chr19-42260697;