rs4808105

Positions:

• chr19-17942531-T-C

Variant summary

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

The NM_001136203.2(CCDC124):​c.160-125T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 1,075,842 control chromosomes in the GnomAD database, including 249,325 homozygotes. 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 0.72 (41003 hom., cov: 32)
  • Exomes 𝑓: 0.67 (208322 hom.)
• Consequence: CCDC124 NM_001136203.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174

Genes affected

CCDC124 (HGNC:25171): (coiled-coil domain containing 124) Enables RNA binding activity. Predicted to be involved in cell division. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC124	NM_001136203.2	c.160-125T>C		intron_variant		ENST00000445755.7	NP_001129675.1
CCDC124	NM_138442.4	c.160-125T>C		intron_variant			NP_612451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC124	ENST00000445755.7	c.160-125T>C		intron_variant		2	NM_001136203.2	ENSP00000408730.1
CCDC124	ENST00000597436.5	c.160-125T>C		intron_variant		1		ENSP00000471455.1
CCDC124	ENST00000596123.1	c.160-125T>C		intron_variant		2		ENSP00000472520.1

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109384 AN: 151928 Hom.: 40938 Cov.: 32

Gnomad AFR AF: 0.923

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.711

GnomAD4 exome AF: 0.667 AC: 615888 AN: 923792 Hom.: 208322 AF XY: 0.665 AC XY: 308946 AN XY: 464526

Gnomad4 AFR exome AF: 0.932

Gnomad4 AMR exome AF: 0.475

Gnomad4 ASJ exome AF: 0.829

Gnomad4 EAS exome AF: 0.476

Gnomad4 SAS exome AF: 0.602

Gnomad4 FIN exome AF: 0.602

Gnomad4 NFE exome AF: 0.678

Gnomad4 OTH exome AF: 0.681

GnomAD4 genome AF: 0.720 AC: 109500 AN: 152050 Hom.: 41003 Cov.: 32 AF XY: 0.710 AC XY: 52788 AN XY: 74302

Gnomad4 AFR AF: 0.923

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.841

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.606

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.674

Gnomad4 OTH AF: 0.714

Alfa AF: 0.692 Hom.: 21396

Bravo AF: 0.726

Asia WGS AF: 0.594 AC: 2064 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs4808105; hg19: chr19-18053340; COSMIC: COSV71490334;