rs10518146

Positions:

• chr4-76332310-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001394954.1(CCDC158):​c.2882+122G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 708,360 control chromosomes in the GnomAD database, including 79 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 0.014 (16 hom., cov: 32)
  • Exomes 𝑓: 0.014 (63 hom.)
• Consequence: CCDC158 NM_001394954.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101

Genes affected

CCDC158 (HGNC:26374): (coiled-coil domain containing 158)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0135 (2057/152220) while in subpopulation NFE AF= 0.0162 (1104/68014). AF 95% confidence interval is 0.0154. There are 16 homozygotes in gnomad4. There are 1014 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC158	NM_001394954.1	c.2882+122G>A		intron_variant		ENST00000682701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC158	ENST00000682701.1	c.2882+122G>A		intron_variant			NM_001394954.1	A1
CCDC158	ENST00000504667.2	n.2748+122G>A		intron_variant, non_coding_transcript_variant		1
CCDC158	ENST00000388914.7	c.2870+122G>A		intron_variant		5		P4

Frequencies

GnomAD3 genomes AF: 0.0135 AC: 2053 AN: 152102 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.00557

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.0257

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0162

Gnomad OTH AF: 0.0115

GnomAD4 exome AF: 0.0139 AC: 7715 AN: 556140 Hom.: 63 AF XY: 0.0135 AC XY: 4059 AN XY: 299754

Gnomad4 AFR exome AF: 0.0118

Gnomad4 AMR exome AF: 0.00353

Gnomad4 ASJ exome AF: 0.0120

Gnomad4 EAS exome AF: 0.0000357

Gnomad4 SAS exome AF: 0.00479

Gnomad4 FIN exome AF: 0.0238

Gnomad4 NFE exome AF: 0.0159

Gnomad4 OTH exome AF: 0.0123

GnomAD4 genome AF: 0.0135 AC: 2057 AN: 152220 Hom.: 16 Cov.: 32 AF XY: 0.0136 AC XY: 1014 AN XY: 74420

Gnomad4 AFR AF: 0.0118

Gnomad4 AMR AF: 0.00556

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00476

Gnomad4 FIN AF: 0.0257

Gnomad4 NFE AF: 0.0162

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0150 Hom.: 2

Bravo AF: 0.0119

Asia WGS AF: 0.00376 AC: 13 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.2
DANN	Benign	0.78

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: rs10518146; hg19: chr4-77253463;