chr19-41579475-C-T

Variant names:

• chr19-41579475-C-T
• rs368535219
• NM_001098506.4:c.547C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001098506.4(CEACAM21):​c.547C>T​(p.Arg183Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000194 in 1,613,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: CEACAM21 NM_001098506.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.52
• Publications: 1 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.102032065).

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.547C>T	p.Arg183Cys	missense	Exon 3 of 7	NP_001091976.3	Q3KPI0-1
	CEACAM21	NM_033543.6		c.547C>T	p.Arg183Cys	missense	Exon 3 of 7	NP_291021.4
	CEACAM21	NM_001288773.3		c.163C>T	p.Arg55Cys	missense	Exon 4 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.547C>T	p.Arg183Cys	missense	Exon 3 of 7	ENSP00000385739.2	Q3KPI0-1
	CEACAM21	ENST00000187608.13	TSL:1	c.547C>T	p.Arg183Cys	missense	Exon 3 of 7	ENSP00000187608.9	Q3KPI0-2
	CEACAM21	ENST00000457737.5	TSL:1	n.*54C>T		non_coding_transcript_exon	Exon 3 of 7	ENSP00000390697.1	Q3KPI0-3

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152104 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.000382

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000173 AC: 43 AN: 249106 AF XY: 0.000148

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000354

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000194 AC: 283 AN: 1461668 Hom.: 0 Cov.: 31 AF XY: 0.000197 AC XY: 143 AN XY: 727106

African (AFR) AF: 0.0000597 AC: 2 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

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

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

European-Finnish (FIN) AF: 0.000131 AC: 7 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000238 AC: 265 AN: 1111844

Other (OTH) AF: 0.000116 AC: 7 AN: 60374

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152222 Hom.: 0 Cov.: 31 AF XY: 0.000175 AC XY: 13 AN XY: 74418

African (AFR) AF: 0.0000481 AC: 2 AN: 41540

American (AMR) AF: 0.0000654 AC: 1 AN: 15294

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68010

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.000320 Hom.: 0

Bravo AF: 0.000178

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000358 AC: 3

ExAC AF: 0.000182 AC: 22

EpiCase AF: 0.000273

EpiControl AF: 0.000356

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	0.27
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	13
DANN	Benign	0.88
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0030	N
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.5
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.096
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.056	T
Vest4		0.14
MVP		0.15
MPC		0.33
ClinPred		0.083	T
GERP RS		-2.0
PromoterAI		-0.019	Neutral
gMVP		0.19
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs368535219; hg19: chr19-42085828; COSMIC: COSV51814804; COSMIC: COSV51814804;