NM_001366385.1:c.2692-182A>G

Variant names:

• chr17-80206788-A-G
• rs4889837
• NM_001366385.1:c.2692-182A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001366385.1(CARD14):​c.2692-182A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 412,262 control chromosomes in the GnomAD database, including 63,297 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (18704 hom., cov: 32)
  • Exomes 𝑓: 0.58 (44593 hom.)
• Consequence: CARD14 NM_001366385.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.236
• Publications: 5 publications found

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]

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 17-80206788-A-G is Benign according to our data. Variant chr17-80206788-A-G is described in ClinVar as Benign. ClinVar VariationId is 1255138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD14	NM_001366385.1	MANE Select	c.2692-182A>G		intron	N/A	NP_001353314.1	Q9BXL6-1
	CARD14	NM_024110.4		c.2692-182A>G		intron	N/A	NP_077015.2	Q9BXL6-1
	CARD14	NR_047566.2		n.2829-182A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD14	ENST00000648509.2	MANE Select	c.2692-182A>G		intron	N/A	ENSP00000498071.1	Q9BXL6-1
	CARD14	ENST00000344227.6	TSL:1	c.2692-182A>G		intron	N/A	ENSP00000344549.2	Q9BXL6-1
	CARD14	ENST00000651672.1		c.2719-182A>G		intron	N/A	ENSP00000499145.1	A0A494C1N2

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72742 AN: 151850 Hom.: 18713 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.481

GnomAD4 exome AF: 0.581 AC: 151252 AN: 260294 Hom.: 44593 Cov.: 3 AF XY: 0.582 AC XY: 78261 AN XY: 134408

African (AFR) AF: 0.298 AC: 2018 AN: 6764

American (AMR) AF: 0.435 AC: 3377 AN: 7768

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 5033 AN: 9096

East Asian (EAS) AF: 0.684 AC: 15071 AN: 22042

South Asian (SAS) AF: 0.572 AC: 5465 AN: 9558

European-Finnish (FIN) AF: 0.562 AC: 12454 AN: 22172

Middle Eastern (MID) AF: 0.556 AC: 1128 AN: 2030

European-Non Finnish (NFE) AF: 0.595 AC: 97784 AN: 164430

Other (OTH) AF: 0.543 AC: 8922 AN: 16434

GnomAD4 genome AF: 0.479 AC: 72742 AN: 151968 Hom.: 18704 Cov.: 32 AF XY: 0.479 AC XY: 35572 AN XY: 74264

African (AFR) AF: 0.282 AC: 11669 AN: 41446

American (AMR) AF: 0.436 AC: 6658 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1900 AN: 3466

East Asian (EAS) AF: 0.573 AC: 2949 AN: 5148

South Asian (SAS) AF: 0.495 AC: 2387 AN: 4824

European-Finnish (FIN) AF: 0.547 AC: 5775 AN: 10550

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.584 AC: 39657 AN: 67942

Other (OTH) AF: 0.480 AC: 1010 AN: 2104

Alfa AF: 0.421 Hom.: 1400

Bravo AF: 0.458

Asia WGS AF: 0.517 AC: 1796 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.33
DANN	Benign	0.10
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs4889837; hg19: chr17-78180587;