rs199801483

Variant names:

• chr19-41577200-C-T
• rs199801483
• NM_001098506.4:c.65C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001098506.4(CEACAM21):​c.65C>T​(p.Ala22Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,613,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: CEACAM21 NM_001098506.4 missense, splice_region
• Scores: Splicing: ADA: 0.0001199
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.863
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0529961).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM21	NM_001098506.4	MANE Select	c.65C>T	p.Ala22Val	missense splice_region	Exon 2 of 7	NP_001091976.3	Q3KPI0-1
	CEACAM21	NM_033543.6		c.65C>T	p.Ala22Val	missense splice_region	Exon 2 of 7	NP_291021.4
	CEACAM21	NM_001288773.3		c.-403C>T		splice_region	Exon 3 of 8	NP_001275702.2	A0A0B4J1W4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM21	ENST00000401445.4	TSL:1 MANE Select	c.65C>T	p.Ala22Val	missense splice_region	Exon 2 of 7	ENSP00000385739.2	Q3KPI0-1
	CEACAM21	ENST00000187608.13	TSL:1	c.65C>T	p.Ala22Val	missense splice_region	Exon 2 of 7	ENSP00000187608.9	Q3KPI0-2
	CEACAM21	ENST00000457737.5	TSL:1	n.65C>T		splice_region non_coding_transcript_exon	Exon 2 of 7	ENSP00000390697.1	Q3KPI0-3

Frequencies

GnomAD3 genomes AF: 0.000269 AC: 41 AN: 152140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000983

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: 0.0000441

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000112 AC: 28 AN: 250222 AF XY: 0.0000958

Gnomad AFR exome AF: 0.000322

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000617

Gnomad OTH exome AF: 0.000494

GnomAD4 exome AF: 0.000103 AC: 150 AN: 1461716 Hom.: 0 Cov.: 33 AF XY: 0.000102 AC XY: 74 AN XY: 727168

African (AFR) AF: 0.000269 AC: 9 AN: 33476

American (AMR) AF: 0.000537 AC: 24 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000354 AC: 2 AN: 5654

European-Non Finnish (NFE) AF: 0.0000890 AC: 99 AN: 1111986

Other (OTH) AF: 0.000265 AC: 16 AN: 60380

GnomAD4 genome AF: 0.000269 AC: 41 AN: 152140 Hom.: 0 Cov.: 32 AF XY: 0.000296 AC XY: 22 AN XY: 74324

African (AFR) AF: 0.000483 AC: 20 AN: 41406

American (AMR) AF: 0.000983 AC: 15 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68036

Other (OTH) AF: 0.00144 AC: 3 AN: 2090

Alfa AF: 0.000181 Hom.: 0

Bravo AF: 0.000366

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000238 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000991 AC: 12

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.1
DANN	Benign	0.73
Eigen	Benign	-0.88
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0038	N
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.96	T
PhyloP100		-0.86
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.088
Sift	Benign	0.36	T
Sift4G	Benign	0.34	T
Vest4		0.037
MVP		0.11
MPC		0.13
ClinPred		0.0097	T
GERP RS		-0.79
gMVP		0.16
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00012
dbscSNV1_RF	Benign	0.042
SpliceAI score (max)		0.010		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: rs199801483; hg19: chr19-42083552;