19-17942531-T-C

Variant names:

• chr19-17942531-T-C
• rs4808105
• NM_001136203.2:c.160-125T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136203.2. 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
	CCDC124	NM_001136203.2	MANE Select	c.160-125T>C		intron	N/A	NP_001129675.1	Q96CT7
	CCDC124	NM_138442.4		c.160-125T>C		intron	N/A	NP_612451.1	Q96CT7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC124	ENST00000445755.7	TSL:2 MANE Select	c.160-125T>C		intron	N/A	ENSP00000408730.1	Q96CT7
	CCDC124	ENST00000597436.5	TSL:1	c.160-125T>C		intron	N/A	ENSP00000471455.1	Q96CT7
	CCDC124	ENST00000873323.1		c.160-125T>C		intron	N/A	ENSP00000543382.1

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

African (AFR) AF: 0.932 AC: 19729 AN: 21166

American (AMR) AF: 0.475 AC: 10881 AN: 22904

Ashkenazi Jewish (ASJ) AF: 0.829 AC: 14291 AN: 17236

East Asian (EAS) AF: 0.476 AC: 15730 AN: 33030

South Asian (SAS) AF: 0.602 AC: 34387 AN: 57074

European-Finnish (FIN) AF: 0.602 AC: 26283 AN: 43680

Middle Eastern (MID) AF: 0.702 AC: 2069 AN: 2948

European-Non Finnish (NFE) AF: 0.678 AC: 464384 AN: 684440

Other (OTH) AF: 0.681 AC: 28134 AN: 41314

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

African (AFR) AF: 0.923 AC: 38349 AN: 41528

American (AMR) AF: 0.557 AC: 8502 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 2919 AN: 3472

East Asian (EAS) AF: 0.508 AC: 2617 AN: 5152

South Asian (SAS) AF: 0.606 AC: 2923 AN: 4822

European-Finnish (FIN) AF: 0.586 AC: 6182 AN: 10558

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45766 AN: 67952

Other (OTH) AF: 0.714 AC: 1505 AN: 2108

Alfa AF: 0.686 Hom.: 35986

Bravo AF: 0.726

Asia WGS AF: 0.594 AC: 2064 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.73
PhyloP100		-0.17
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: rs4808105; hg19: chr19-18053340; COSMIC: COSV71490334;