19-41686913-C-A

Variant names:

• chr19-41686913-C-A
• rs148268768
• NM_001291485.2:c.373G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001291485.2(CEACAM7):​c.373G>T​(p.Val125Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000338 in 1,554,988 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V125I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (2 hom.)
• Consequence: CEACAM7 NM_001291485.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 2 publications found

Genes affected

CEACAM7 (HGNC:1819): (CEA cell adhesion molecule 7) This gene encodes a cell surface glycoprotein and member of the carcinoembryonic antigen (CEA) family of proteins. Expression of this gene may be downregulated in colon and rectal cancer. Additionally, lower expression levels of this gene may be predictive of rectal cancer recurrence. This gene is present in a CEA family gene cluster on chromosome 19. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009832591).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291485.2. 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
	CEACAM7	NM_001291485.2	MANE Select	c.373G>T	p.Val125Phe	missense	Exon 2 of 5	NP_001278414.1	Q14002-1
	CEACAM7	NM_006890.5		c.373G>T	p.Val125Phe	missense	Exon 2 of 5	NP_008821.2	Q14002-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM7	ENST00000401731.6	TSL:2 MANE Select	c.373G>T	p.Val125Phe	missense	Exon 2 of 5	ENSP00000385932.1	Q14002-1
	CEACAM7	ENST00000006724.7	TSL:1	c.373G>T	p.Val125Phe	missense	Exon 2 of 5	ENSP00000006724.3	Q14002-1
	CEACAM7	ENST00000602225.1	TSL:1	c.373G>T	p.Val125Phe	missense	Exon 2 of 3	ENSP00000469597.1	Q14002-2

Frequencies

GnomAD3 genomes AF: 0.00195 AC: 297 AN: 152128 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00635

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.000524 AC: 107 AN: 204390 AF XY: 0.000429

Gnomad AFR exome AF: 0.00606

Gnomad AMR exome AF: 0.000356

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000103

Gnomad OTH exome AF: 0.000417

GnomAD4 exome AF: 0.000164 AC: 230 AN: 1402742 Hom.: 2 Cov.: 31 AF XY: 0.000146 AC XY: 101 AN XY: 693276

African (AFR) AF: 0.00614 AC: 191 AN: 31126

American (AMR) AF: 0.000353 AC: 12 AN: 33950

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39310

South Asian (SAS) AF: 0.00 AC: 0 AN: 75416

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51076

Middle Eastern (MID) AF: 0.000182 AC: 1 AN: 5484

European-Non Finnish (NFE) AF: 9.20e-7 AC: 1 AN: 1086476

Other (OTH) AF: 0.000432 AC: 25 AN: 57806

GnomAD4 genome AF: 0.00194 AC: 296 AN: 152246 Hom.: 1 Cov.: 32 AF XY: 0.00188 AC XY: 140 AN XY: 74446

African (AFR) AF: 0.00631 AC: 262 AN: 41528

American (AMR) AF: 0.00150 AC: 23 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68016

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.000698 Hom.: 0

Bravo AF: 0.00179

ESP6500AA AF: 0.00726 AC: 32

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000577 AC: 70

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	9.1
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.0096	N
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.0098	T
MetaSVM	Benign	-0.45	T
PhyloP100		-1.7
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.28
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Vest4		0.52
MVP		0.41
MPC		0.12
ClinPred		0.11	T
GERP RS		-3.4
gMVP		0.54
Mutation Taster		=98/2	polymorphism

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: rs148268768; hg19: chr19-42190844;