17-59670178-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004859.4(CLTC):c.2292+1238T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,180 control chromosomes in the GnomAD database, including 1,662 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 0.12 (1662 hom., cov: 32)
• Consequence: CLTC NM_004859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.658

Genes affected

CLTC (HGNC:2092): (clathrin heavy chain) Clathrin is a major protein component of the cytoplasmic face of intracellular organelles, called coated vesicles and coated pits. These specialized organelles are involved in the intracellular trafficking of receptors and endocytosis of a variety of macromolecules. The basic subunit of the clathrin coat is composed of three heavy chains and three light chains. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLTC	NM_004859.4	c.2292+1238T>G		intron_variant		ENST00000269122.8
CLTC	NM_001288653.2	c.2304+1238T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLTC	ENST00000269122.8	c.2292+1238T>G		intron_variant		1	NM_004859.4	P4

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17651 AN: 152064 Hom.: 1653 Cov.: 32

Gnomad AFR AF: 0.0610

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0968

Gnomad OTH AF: 0.114

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.116 AC: 17655 AN: 152180 Hom.: 1662 Cov.: 32 AF XY: 0.124 AC XY: 9196 AN XY: 74402

Gnomad4 AFR AF: 0.0609

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.0968

Gnomad4 OTH AF: 0.124

Alfa AF: 0.105 Hom.: 1467

Bravo AF: 0.108

Asia WGS AF: 0.400 AC: 1391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.2
Dann	Benign	0.52

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: rs10515171; hg19: chr17-57747539;