19-41761981-T-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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

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]

ENSG00000268833 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEACAM6	NM_002483.7	c.716T>G	p.Val239Gly	missense_variant	Exon 4 of 6	ENST00000199764.7	NP_002474.4
CEACAM6	XM_011526990.3	c.716T>G	p.Val239Gly	missense_variant	Exon 4 of 5		XP_011525292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEACAM6	ENST00000199764.7	c.716T>G	p.Val239Gly	missense_variant	Exon 4 of 6	1	NM_002483.7	ENSP00000199764.6
ENSG00000268833	ENST00000601409.1	n.384-3900A>C		intron_variant	Intron 1 of 1	4

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

Gnomad4 AFR exome AF: 0.295

Gnomad4 AMR exome AF: 0.472

Gnomad4 ASJ exome AF: 0.614

Gnomad4 EAS exome AF: 0.454

Gnomad4 SAS exome AF: 0.611

Gnomad4 FIN exome AF: 0.543

Gnomad4 NFE exome AF: 0.579

Gnomad4 OTH exome AF: 0.560

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

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.530

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.523

Alfa AF: 0.521 Hom.: 11915

Bravo AF: 0.476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
CADD	Benign	0.25
MetaRNN	Benign	0.0031	T
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

Publications

LitVar

Other links and lift over

dbSNP: rs11548735; hg19: -;