Genetic Variant NM_001098506.4:c.592G>A (chr19-41579520-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001098506.4(CEACAM21):c.592G>A(p.Val198Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,612,658 control chromosomes in the GnomAD database, including 65,864 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 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 0.35 ( 11036 hom., cov: 31)

Exomes 𝑓: 0.27 ( 54828 hom. )

Consequence

CEACAM21
NM_001098506.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.270

Publications

49 publications found

Variant links:

Genes affected

CEACAM21 (HGNC:28834): (CEA cell adhesion molecule 21) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

CEACAM21 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0048744977).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098506.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CEACAM21	NM_001098506.4	MANE Select	c.592G>A	p.Val198Met	missense	Exon 3 of 7	NP_001091976.3	Q3KPI0-1
CEACAM21	NM_033543.6		c.592G>A	p.Val198Met	missense	Exon 3 of 7	NP_291021.4
CEACAM21	NM_001288773.3		c.208G>A	p.Val70Met	missense	Exon 4 of 8	NP_001275702.2	A0A0B4J1W4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CEACAM21	ENST00000401445.4	TSL:1 MANE Select	c.592G>A	p.Val198Met	missense	Exon 3 of 7	ENSP00000385739.2	Q3KPI0-1
CEACAM21	ENST00000187608.13	TSL:1	c.592G>A	p.Val198Met	missense	Exon 3 of 7	ENSP00000187608.9	Q3KPI0-2
CEACAM21	ENST00000457737.5	TSL:1	n.*99G>A		non_coding_transcript_exon	Exon 3 of 7	ENSP00000390697.1	Q3KPI0-3

Frequencies

GnomAD3 genomes

AF:

0.352

AC:

53468

AN:

151726

Hom.:

11011

Cov.:

show subpopulations

Gnomad AFR

AF:

0.571

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.232

Gnomad ASJ

AF:

0.299

Gnomad EAS

AF:

0.395

Gnomad SAS

AF:

0.307

Gnomad FIN

AF:

0.331

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.256

Gnomad OTH

AF:

0.324

GnomAD4 exome

AF:

0.266

AC:

388848

AN:

1460814

Hom.:

54828

Cov.:

AF XY:

0.267

AC XY:

193919

AN XY:

726576

show subpopulations

African (AFR)

AF:

0.582

AC:

19484

AN:

33472

American (AMR)

AF:

0.174

AC:

7743

AN:

44594

Ashkenazi Jewish (ASJ)

AF:

0.293

AC:

7669

AN:

26134

East Asian (EAS)

AF:

0.434

AC:

17201

AN:

39668

South Asian (SAS)

AF:

0.295

AC:

25386

AN:

86186

European-Finnish (FIN)

AF:

0.324

AC:

17304

AN:

53342

Middle Eastern (MID)

AF:

0.254

AC:

1461

AN:

5762

European-Non Finnish (NFE)

AF:

0.248

AC:

275192

AN:

1111324

Other (OTH)

AF:

0.289

AC:

17408

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

18602

37204

55806

74408

93010

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9532

19064

28596

38128

47660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.353

AC:

53536

AN:

151844

Hom.:

11036

Cov.:

AF XY:

0.353

AC XY:

26197

AN XY:

74196

show subpopulations

African (AFR)

AF:

0.571

AC:

23615

AN:

41342

American (AMR)

AF:

0.231

AC:

3532

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.299

AC:

1036

AN:

3470

East Asian (EAS)

AF:

0.395

AC:

2035

AN:

5156

South Asian (SAS)

AF:

0.306

AC:

1472

AN:

4808

European-Finnish (FIN)

AF:

0.331

AC:

3487

AN:

10546

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.256

AC:

17399

AN:

67948

Other (OTH)

AF:

0.324

AC:

680

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1606

3212

4817

6423

8029

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

506

1012

1518

2024

2530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.280

Hom.:

31754

Bravo

AF:

0.354

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.5

(source)

MetaRNN

Benign

0.0049

PhyloP100

-0.27

Sift4G

Benign

0.12

Vest4

0.057

PromoterAI

0.018

Neutral

(source)

gMVP

0.17

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over