Genetic Variant CXADR:c.1017+4525A>T (chr21-17570136-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001207066.2(CXADR):c.1017+4525A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 985,188 control chromosomes in the GnomAD database, including 7,880 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.11 ( 971 hom., cov: 32)

Exomes 𝑓: 0.13 ( 6909 hom. )

Consequence

CXADR
NM_001207066.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.663

Publications

1 publications found

Variant links:

Genes affected

CXADR (HGNC:2559): (CXADR Ig-like cell adhesion molecule) The protein encoded by this gene is a type I membrane receptor for group B coxsackieviruses and subgroup C adenoviruses. Several transcript variants encoding different isoforms have been found for this gene. Pseudogenes of this gene are found on chromosomes 15, 18, and 21. [provided by RefSeq, May 2011]

CXADR 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 (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001207066.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CXADR	NM_001207066.2		c.1017+4525A>T	intron	N/A	NP_001193995.1	P78310-6
CXADR	NM_001338.5	MANE Select	c.*4444A>T	downstream_gene	N/A	NP_001329.1	P78310-1
CXADR	NM_001207063.2		c.*4521A>T	downstream_gene	N/A	NP_001193992.1	P78310-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXADR	ENST00000400169.1	TSL:5	c.1017+4525A>T		intron	N/A	ENSP00000383033.1	P78310-6
	CXADR	ENST00000284878.12	TSL:1 MANE Select	c.*4444A>T		downstream_gene	N/A	ENSP00000284878.7	P78310-1

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16715

AN:

152076

Hom.:

969

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.183

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.0886

Gnomad FIN

AF:

0.0773

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.118

GnomAD4 exome

AF:

0.128

AC:

106299

AN:

832994

Hom.:

6909

Cov.:

AF XY:

0.128

AC XY:

49300

AN XY:

384662

show subpopulations

African (AFR)

AF:

0.109

AC:

1727

AN:

15784

American (AMR)

AF:

0.0732

AC:

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

906

AN:

5152

East Asian (EAS)

AF:

0.00110

AC:

AN:

3630

South Asian (SAS)

AF:

0.0898

AC:

1478

AN:

16460

European-Finnish (FIN)

AF:

0.0906

AC:

AN:

276

Middle Eastern (MID)

AF:

0.137

AC:

222

AN:

1620

European-Non Finnish (NFE)

AF:

0.129

AC:

98559

AN:

761792

Other (OTH)

AF:

0.121

AC:

3306

AN:

27296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

4814

9629

14443

19258

24072

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4916

9832

14748

19664

24580

<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:

0.110

AC:

16729

AN:

152194

Hom.:

971

Cov.:

AF XY:

0.107

AC XY:

7987

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.109

AC:

4537

AN:

41528

American (AMR)

AF:

0.103

AC:

1578

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.183

AC:

634

AN:

3464

East Asian (EAS)

AF:

0.00193

AC:

AN:

5182

South Asian (SAS)

AF:

0.0899

AC:

434

AN:

4826

European-Finnish (FIN)

AF:

0.0773

AC:

819

AN:

10596

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.122

AC:

8326

AN:

68002

Other (OTH)

AF:

0.117

AC:

248

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

763

1526

2290

3053

3816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

368

552

736

920

<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:

0.108

Hom.:

111

Bravo

AF:

0.112

Asia WGS

AF:

0.0440

AC:

154

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.41

(source)

DANN

Benign

0.84

PhyloP100

-0.66

Mutation Taster

=100/0

polymorphism (auto)

(source)

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