X-49238748-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

CCDC22 Gene-Disease associations (from GenCC):

• Ritscher-Schinzel syndrome 2

  Inheritance: XL Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P
• Ritscher-Schinzel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• epilepsy

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014008.5. 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
	CCDC22	NM_014008.5	MANE Select	c.228+1485C>T		intron	N/A	NP_054727.1	O60826

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC22	ENST00000376227.4	TSL:1 MANE Select	c.228+1485C>T		intron	N/A	ENSP00000365401.3	O60826
	CCDC22	ENST00000960401.1		c.228+1485C>T		intron	N/A	ENSP00000630460.1
	CCDC22	ENST00000904959.1		c.228+1485C>T		intron	N/A	ENSP00000575018.1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 57227 AN: 109338 Hom.: 13142 Cov.: 22

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

African (AFR) AF: 0.149 AC: 4501 AN: 30180

American (AMR) AF: 0.499 AC: 5174 AN: 10365

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2060 AN: 2603

East Asian (EAS) AF: 0.332 AC: 1130 AN: 3404

South Asian (SAS) AF: 0.659 AC: 1676 AN: 2543

European-Finnish (FIN) AF: 0.642 AC: 3583 AN: 5579

Middle Eastern (MID) AF: 0.712 AC: 151 AN: 212

European-Non Finnish (NFE) AF: 0.720 AC: 37700 AN: 52378

Other (OTH) AF: 0.566 AC: 834 AN: 1474

Alfa AF: 0.592 Hom.: 4523

Bravo AF: 0.490

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.15
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs5952519; hg19: chrX-49095215;