chr4-185458293-C-T

Variant names:

• chr4-185458293-C-T
• rs372188187
• NM_152775.4:c.2294G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_152775.4(CCDC110):​c.2294G>A​(p.Arg765Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,593,692 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000045 (3 hom.)
• Consequence: CCDC110 NM_152775.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.318
• Publications: 4 publications found

Genes affected

CCDC110 (HGNC:28504): (coiled-coil domain containing 110) Predicted to be located in nucleus. Predicted to be active in cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018425226).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152775.4. 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
	CCDC110	NM_152775.4	MANE Select	c.2294G>A	p.Arg765Gln	missense	Exon 6 of 7	NP_689988.1	Q8TBZ0-1
	CCDC110	NM_001145411.2		c.2183G>A	p.Arg728Gln	missense	Exon 5 of 6	NP_001138883.1	Q8TBZ0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC110	ENST00000307588.8	TSL:1 MANE Select	c.2294G>A	p.Arg765Gln	missense	Exon 6 of 7	ENSP00000306776.3	Q8TBZ0-1
	CCDC110	ENST00000393540.7	TSL:1	c.2183G>A	p.Arg728Gln	missense	Exon 5 of 6	ENSP00000377172.3	Q8TBZ0-2
	CCDC110	ENST00000510617.5	TSL:5	c.2294G>A	p.Arg765Gln	missense	Exon 6 of 7	ENSP00000427246.1	E7EUS2

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152046 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000100 AC: 23 AN: 229422 AF XY: 0.0000564

Gnomad AFR exome AF: 0.000577

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000761

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000934

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000451 AC: 65 AN: 1441528 Hom.: 3 Cov.: 34 AF XY: 0.0000572 AC XY: 41 AN XY: 716440

African (AFR) AF: 0.000374 AC: 12 AN: 32120

American (AMR) AF: 0.0000255 AC: 1 AN: 39214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25256

East Asian (EAS) AF: 0.000815 AC: 32 AN: 39264

South Asian (SAS) AF: 0.000135 AC: 11 AN: 81442

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.00000633 AC: 7 AN: 1106124

Other (OTH) AF: 0.0000336 AC: 2 AN: 59458

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152164 Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10 AN XY: 74390

African (AFR) AF: 0.000289 AC: 12 AN: 41530

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.000963 AC: 5 AN: 5192

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4808

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.000234 Hom.: 0

Bravo AF: 0.000174

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000115 AC: 14

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.92
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.32
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.019
Sift	Benign	0.091	T
Sift4G	Benign	0.38	T
Polyphen		0.14	B
Vest4		0.25
MVP		0.27
MPC		0.10
ClinPred		0.022	T
GERP RS		1.9
PromoterAI		-0.016	Neutral
Varity_R		0.039
gMVP		0.021
Mutation Taster		=100/0	polymorphism

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: rs372188187; hg19: chr4-186379447; COSMIC: COSV56874159; COSMIC: COSV56874159;