17-80181089-TAAAA-TAAAAAAAAA

Variant names:

• chr17-80181089-T-TAAAAA
• rs60307812
• NM_001366385.1:c.-20-320_-20-316dupAAAAA

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1 BS2_Supporting

The NM_001366385.1(CARD14):​c.-20-320_-20-316dupAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00035 (1 hom., cov: 20)
• Consequence: CARD14 NM_001366385.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.511

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000353 (50/141482) while in subpopulation EAS AF= 0.00164 (8/4864). AF 95% confidence interval is 0.000818. There are 1 homozygotes in gnomad4. There are 27 alleles in male gnomad4 subpopulation. Median coverage is 20. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 50 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD14	NM_001366385.1	c.-20-320_-20-316dupAAAAA		intron_variant	Intron 4 of 23	ENST00000648509.2	NP_001353314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARD14	ENST00000648509.2	c.-20-330_-20-329insAAAAA		intron_variant	Intron 4 of 23		NM_001366385.1	ENSP00000498071.1

Frequencies

GnomAD3 genomes AF: 0.000354 AC: 50 AN: 141432 Hom.: 1 Cov.: 20

Gnomad AFR AF: 0.000414

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000710

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00164

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000476

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000310

Gnomad OTH AF: 0.000514

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.000353 AC: 50 AN: 141482 Hom.: 1 Cov.: 20 AF XY: 0.000395 AC XY: 27 AN XY: 68340

Gnomad4 AFR AF: 0.000413

Gnomad4 AMR AF: 0.0000710

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00164

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000476

Gnomad4 NFE AF: 0.000310

Gnomad4 OTH AF: 0.000511

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs60307812; hg19: chr17-78154888;