19-41761981-T-G

Variant names:

• chr19-41761981-T-G
• rs11548735
• NM_002483.7:c.716T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002483.7(CEACAM6):​c.716T>G​(p.Val239Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 1,613,162 control chromosomes in the GnomAD database, including 256,378 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.49 (19200 hom., cov: 31)
  • Exomes 𝑓: 0.57 (237178 hom.)
• Consequence: CEACAM6 NM_002483.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149
• Publications: 32 publications found

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]

CEACAM6 Gene-Disease associations (from GenCC):

• cystic fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000268833 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030976832).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002483.7. 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
	CEACAM6	NM_002483.7	MANE Select	c.716T>G	p.Val239Gly	missense	Exon 4 of 6	NP_002474.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM6	ENST00000199764.7	TSL:1 MANE Select	c.716T>G	p.Val239Gly	missense	Exon 4 of 6	ENSP00000199764.6	P40199
	CEACAM6	ENST00000890871.1		c.707T>G	p.Val236Gly	missense	Exon 4 of 6	ENSP00000560930.1
	CEACAM6	ENST00000943164.1		c.617T>G	p.Val206Gly	missense	Exon 4 of 6	ENSP00000613223.1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 73857 AN: 151418 Hom.: 19197 Cov.: 31

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.528

GnomAD4 exome AF: 0.567 AC: 828233 AN: 1461626 Hom.: 237178 Cov.: 55 AF XY: 0.570 AC XY: 414782 AN XY: 727132

African (AFR) AF: 0.295 AC: 9875 AN: 33478

American (AMR) AF: 0.472 AC: 21101 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 16059 AN: 26134

East Asian (EAS) AF: 0.454 AC: 18043 AN: 39700

South Asian (SAS) AF: 0.611 AC: 52717 AN: 86238

European-Finnish (FIN) AF: 0.543 AC: 28998 AN: 53414

Middle Eastern (MID) AF: 0.731 AC: 4215 AN: 5768

European-Non Finnish (NFE) AF: 0.579 AC: 643409 AN: 1111788

Other (OTH) AF: 0.560 AC: 33816 AN: 60388

GnomAD4 genome AF: 0.488 AC: 73878 AN: 151536 Hom.: 19200 Cov.: 31 AF XY: 0.488 AC XY: 36092 AN XY: 74006

African (AFR) AF: 0.297 AC: 12287 AN: 41344

American (AMR) AF: 0.505 AC: 7697 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2107 AN: 3464

East Asian (EAS) AF: 0.423 AC: 2173 AN: 5142

South Asian (SAS) AF: 0.590 AC: 2841 AN: 4812

European-Finnish (FIN) AF: 0.530 AC: 5545 AN: 10460

Middle Eastern (MID) AF: 0.678 AC: 198 AN: 292

European-Non Finnish (NFE) AF: 0.580 AC: 39307 AN: 67764

Other (OTH) AF: 0.523 AC: 1102 AN: 2108

Alfa AF: 0.524 Hom.: 17102

Bravo AF: 0.476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
CADD	Benign	0.25
MetaRNN	Benign	0.0031	T
PhyloP100		-0.15
Sift4G	Benign	0.37	T
Vest4		0.083
gMVP		0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11548735;