dbSNP rs146678380: CARD14:c.2569+4T>C (chr17-80205209-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001366385.1(CARD14):c.2569+4T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00258 in 1,608,286 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 8 hom. )

Consequence

CARD14
NM_001366385.1 splice_region, intron

Scores

Splicing: ADA: 0.00007751

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.84

Publications

0 publications found

Variant links:

Genes affected

CARD14 (HGNC:16446): (caspase recruitment domain family member 14) This gene encodes a caspase recruitment domain-containing protein that is a member of the membrane-associated guanylate kinase (MAGUK) family of proteins. Members of this protein family are scaffold proteins that are involved in a diverse array of cellular processes including cellular adhesion, signal transduction and cell polarity control. This protein has been shown to specifically interact with BCL10, a protein known to function as a positive regulator of cell apoptosis and NF-kappaB activation. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2012]

CARD14 links:

ENSG00000262580 (HGNC:):

ENSG00000262580 links:

SGSH (HGNC:10818): (N-sulfoglucosamine sulfohydrolase) This gene encodes the enzyme sulfamidase; one of several enzymes involved in the lysosomal degradation of heparan sulfate. Mutations in this gene are associated with the lysosomal storage disease mucopolysaccaridosis IIIA, also known as Sanfilippo syndrome A, which results from impaired degradation of heparan sulfate. Transcripts of varying sizes have been reported but their biological validity has not been determined. [provided by RefSeq, Jun 2017]

SGSH Gene-Disease associations (from GenCC):

mucopolysaccharidosis type 3A
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, Myriad Women’s Health, PanelApp Australia, Genomics England PanelApp, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

SGSH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 17-80205209-T-C is Benign according to our data. Variant chr17-80205209-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 527886.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00184 (280/152234) while in subpopulation NFE AF = 0.00325 (221/67986). AF 95% confidence interval is 0.0029. There are 2 homozygotes in GnomAd4. There are 123 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 280 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366385.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CARD14	NM_001366385.1	MANE Select	c.2569+4T>C	splice_region intron	N/A	NP_001353314.1	Q9BXL6-1
CARD14	NM_024110.4		c.2569+4T>C	splice_region intron	N/A	NP_077015.2	Q9BXL6-1
CARD14	NR_047566.2		n.2706+4T>C	splice_region intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CARD14	ENST00000648509.2	MANE Select	c.2569+4T>C	splice_region intron	N/A	ENSP00000498071.1	Q9BXL6-1
CARD14	ENST00000344227.6	TSL:1	c.2569+4T>C	splice_region intron	N/A	ENSP00000344549.2	Q9BXL6-1
CARD14	ENST00000651672.1		c.2596+4T>C	splice_region intron	N/A	ENSP00000499145.1	A0A494C1N2

Frequencies

GnomAD3 genomes

AF:

0.00184

AC:

280

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00325

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00176

AC:

435

AN:

246506

AF XY:

0.00196

show subpopulations

Gnomad AFR exome

AF:

0.000309

Gnomad AMR exome

AF:

0.000675

Gnomad ASJ exome

AF:

0.00320

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00104

Gnomad NFE exome

AF:

0.00278

Gnomad OTH exome

AF:

0.00234

GnomAD4 exome

AF:

0.00266

AC:

3876

AN:

1456052

Hom.:

Cov.:

AF XY:

0.00266

AC XY:

1924

AN XY:

723682

show subpopulations

African (AFR)

AF:

0.000479

AC:

AN:

33418

American (AMR)

AF:

0.000948

AC:

AN:

44296

Ashkenazi Jewish (ASJ)

AF:

0.00283

AC:

AN:

25806

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39612

South Asian (SAS)

AF:

0.00122

AC:

105

AN:

85824

European-Finnish (FIN)

AF:

0.000699

AC:

AN:

52942

Middle Eastern (MID)

AF:

0.00192

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.00312

AC:

3460

AN:

1108314

Other (OTH)

AF:

0.00218

AC:

131

AN:

60096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

194

388

583

777

971

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

134

268

402

536

670

<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:

0.00184

AC:

280

AN:

152234

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

123

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.000433

AC:

AN:

41540

American (AMR)

AF:

0.00118

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00104

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00325

AC:

221

AN:

67986

Other (OTH)

AF:

0.00237

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00231

Hom.:

Bravo

AF:

0.00186

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Autoinflammatory syndrome (1)

Pityriasis rubra pilaris;C1864497:Psoriasis 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.0030

(source)

DANN

Benign

0.86

PhyloP100

-3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000078

dbscSNV1_RF

Benign

0.0020

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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