X-49238748-C-T

Variant names:

• chrX-49238748-C-T
• rs5952519
• NM_014008.5:c.228+1485C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014008.5(CCDC22):​c.228+1485C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 109,394 control chromosomes in the GnomAD database, including 13,138 homozygotes. There are 16,577 hemizygotes in GnomAD. 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 0.52 (13138 hom., 16577 hem., cov: 22)
• Consequence: CCDC22 NM_014008.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

Genes affected

CCDC22 (HGNC:28909): (coiled-coil domain containing 22) This gene encodes a protein containing a coiled-coil domain. The encoded protein functions in the regulation of NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) by interacting with COMMD (copper metabolism Murr1 domain-containing) proteins. The mouse orthologous protein has been shown to bind copines, which are calcium-dependent, membrane-binding proteins that may function in calcium signaling. This human gene has been identified as a novel candidate gene for syndromic X-linked intellectual disability. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC22	NM_014008.5	c.228+1485C>T		intron_variant	Intron 2 of 16	ENST00000376227.4	NP_054727.1
CCDC22	XM_005272599.5	c.228+1485C>T		intron_variant	Intron 2 of 16		XP_005272656.1
CCDC22	XR_430506.4	n.395+1485C>T		intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC22	ENST00000376227.4	c.228+1485C>T		intron_variant	Intron 2 of 16	1	NM_014008.5	ENSP00000365401.3
CCDC22	ENST00000490300.1	n.371+1485C>T		intron_variant	Intron 1 of 4	3
CCDC22	ENST00000496651.5	n.369+1485C>T		intron_variant	Intron 2 of 5	3

Frequencies

GnomAD3 genomes AF: 0.523 AC: 57227 AN: 109338 Hom.: 13142 Cov.: 22 AF XY: 0.521 AC XY: 16557 AN XY: 31790

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.523 AC: 57225 AN: 109394 Hom.: 13138 Cov.: 22 AF XY: 0.520 AC XY: 16577 AN XY: 31856

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.791

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.659

Gnomad4 FIN AF: 0.642

Gnomad4 NFE AF: 0.720

Gnomad4 OTH AF: 0.566

Alfa AF: 0.592 Hom.: 4523

Bravo AF: 0.490

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.15

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5952519; hg19: chrX-49095215;