NM_152612.3:c.73-8C>T

Variant names:

• chr22-21634014-C-T
• rs115833761
• NM_152612.3:c.73-8C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_152612.3(CCDC116):​c.73-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 1,594,220 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0071 (18 hom., cov: 33)
  • Exomes 𝑓: 0.00069 (12 hom.)
• Consequence: CCDC116 NM_152612.3 splice_region, intron
• Scores: Splicing: ADA: 0.00009740
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.456
• Publications: 0 publications found

Genes affected

CCDC116 (HGNC:26688): (coiled-coil domain containing 116) Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 22-21634014-C-T is Benign according to our data. Variant chr22-21634014-C-T is described in ClinVar as [Benign]. Clinvar id is 710988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00711 (1083/152370) while in subpopulation AFR AF = 0.0252 (1047/41590). AF 95% confidence interval is 0.0239. There are 18 homozygotes in GnomAd4. There are 507 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC116	NM_152612.3	c.73-8C>T		splice_region_variant, intron_variant	Intron 2 of 4	ENST00000292779.4	NP_689825.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC116	ENST00000292779.4	c.73-8C>T		splice_region_variant, intron_variant	Intron 2 of 4	1	NM_152612.3	ENSP00000292779.3
CCDC116	ENST00000607942.5	c.73-8C>T		splice_region_variant, intron_variant	Intron 2 of 3	2		ENSP00000476296.1
CCDC116	ENST00000425975.1	c.271-8C>T		splice_region_variant, intron_variant	Intron 2 of 2	4		ENSP00000401637.1

Frequencies

GnomAD3 genomes AF: 0.00711 AC: 1083 AN: 152252 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.0252

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00193 AC: 452 AN: 233918 AF XY: 0.00156

Gnomad AFR exome AF: 0.0258

Gnomad AMR exome AF: 0.000932

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000190

Gnomad OTH exome AF: 0.000701

GnomAD4 exome AF: 0.000686 AC: 989 AN: 1441850 Hom.: 12 Cov.: 31 AF XY: 0.000615 AC XY: 440 AN XY: 715346

African (AFR) AF: 0.0262 AC: 870 AN: 33188

American (AMR) AF: 0.000900 AC: 39 AN: 43310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24388

East Asian (EAS) AF: 0.00 AC: 0 AN: 39592

South Asian (SAS) AF: 0.0000243 AC: 2 AN: 82468

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52400

Middle Eastern (MID) AF: 0.00119 AC: 6 AN: 5030

European-Non Finnish (NFE) AF: 0.00000817 AC: 9 AN: 1101936

Other (OTH) AF: 0.00106 AC: 63 AN: 59538

GnomAD4 genome AF: 0.00711 AC: 1083 AN: 152370 Hom.: 18 Cov.: 33 AF XY: 0.00680 AC XY: 507 AN XY: 74512

African (AFR) AF: 0.0252 AC: 1047 AN: 41590

American (AMR) AF: 0.00176 AC: 27 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68036

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00512 Hom.: 5

Bravo AF: 0.00798

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 08, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	11
DANN	Benign	0.72
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000097
dbscSNV1_RF	Benign	0.028
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: rs115833761; hg19: chr22-21988303;