rs117318560

Variant names:

• chr16-1434535-C-T
• rs117318560
• NM_001143980.3:c.1878-1G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001143980.3(CCDC154):​c.1878-1G>A variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00491 in 1,545,066 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0040 (4 hom., cov: 34)
  • Exomes 𝑓: 0.0050 (29 hom.)
• Consequence: CCDC154 NM_001143980.3 splice_acceptor, intron
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.94
• Publications: 5 publications found

Genes affected

CCDC154 (HGNC:34454): (coiled-coil domain containing 154) Predicted to be involved in bone mineralization involved in bone maturation. Predicted to act upstream of or within bone resorption; odontogenesis of dentin-containing tooth; and tooth eruption. Predicted to be located in early endosome. [provided by Alliance of Genome Resources, Apr 2022]

PERCC1 (HGNC:52293): (proline and glutamate rich with coiled coil 1) Predicted to be involved in digestive tract morphogenesis and enteroendocrine cell differentiation. Implicated in congenital diarrhea. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 16-1434535-C-T is Benign according to our data. Variant chr16-1434535-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2645898.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143980.3. 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
	CCDC154	NM_001143980.3	MANE Select	c.1878-1G>A		splice_acceptor intron	N/A	NP_001137452.1	A6NI56
	PERCC1	NM_001365310.2	MANE Select	c.*1138C>T		downstream_gene	N/A	NP_001352239.1	A0A1W2PR82

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC154	ENST00000389176.4	TSL:5 MANE Select	c.1878-1G>A		splice_acceptor intron	N/A	ENSP00000373828.4	A6NI56
	CCDC154	ENST00000409671.5	TSL:1	c.1443-1G>A		splice_acceptor intron	N/A	ENSP00000386744.1	B7ZBA8
	CCDC154	ENST00000463299.2	TSL:1	n.323-1G>A		splice_acceptor intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00402 AC: 611 AN: 152158 Hom.: 4 Cov.: 34

Gnomad AFR AF: 0.000966

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00556

Gnomad OTH AF: 0.00622

GnomAD2 exomes AF: 0.00468 AC: 698 AN: 149228 AF XY: 0.00466

Gnomad AFR exome AF: 0.00141

Gnomad AMR exome AF: 0.00404

Gnomad ASJ exome AF: 0.0224

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000589

Gnomad NFE exome AF: 0.00507

Gnomad OTH exome AF: 0.00795

GnomAD4 exome AF: 0.00500 AC: 6970 AN: 1392792 Hom.: 29 Cov.: 47 AF XY: 0.00493 AC XY: 3386 AN XY: 686672

African (AFR) AF: 0.000857 AC: 27 AN: 31510

American (AMR) AF: 0.00407 AC: 145 AN: 35586

Ashkenazi Jewish (ASJ) AF: 0.0239 AC: 598 AN: 25040

East Asian (EAS) AF: 0.00 AC: 0 AN: 35676

South Asian (SAS) AF: 0.00286 AC: 226 AN: 78998

European-Finnish (FIN) AF: 0.000875 AC: 40 AN: 45690

Middle Eastern (MID) AF: 0.00742 AC: 39 AN: 5258

European-Non Finnish (NFE) AF: 0.00513 AC: 5523 AN: 1077272

Other (OTH) AF: 0.00644 AC: 372 AN: 57762

GnomAD4 genome AF: 0.00402 AC: 612 AN: 152274 Hom.: 4 Cov.: 34 AF XY: 0.00365 AC XY: 272 AN XY: 74466

African (AFR) AF: 0.000963 AC: 40 AN: 41548

American (AMR) AF: 0.00333 AC: 51 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0262 AC: 91 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4832

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10626

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00556 AC: 378 AN: 67992

Other (OTH) AF: 0.00616 AC: 13 AN: 2112

Alfa AF: 0.00541 Hom.: 4

Bravo AF: 0.00452

ExAC AF: 0.00439 AC: 125

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	25
DANN	Uncertain	0.99
Eigen	Pathogenic	0.83
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.95	D
PhyloP100		1.9
GERP RS		4.9
Mutation Taster		=21/79	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.86
SpliceAI score (max)		0.81		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.81		Position offset: -1

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

Other links and lift over

dbSNP: rs117318560; hg19: chr16-1484536;