NM_004859.4:c.2292+1238T>G

Variant names:

• chr17-59670178-T-G
• rs10515171
• NM_004859.4:c.2292+1238T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

CLTC Gene-Disease associations (from GenCC):

• intellectual disability, autosomal dominant 56

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Illumina
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004859.4. 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
	CLTC	NM_004859.4	MANE Select	c.2292+1238T>G		intron	N/A	NP_004850.1
	CLTC	NM_001288653.2		c.2304+1238T>G		intron	N/A	NP_001275582.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLTC	ENST00000269122.8	TSL:1 MANE Select	c.2292+1238T>G		intron	N/A	ENSP00000269122.3
	CLTC	ENST00000393043.5	TSL:1	c.2292+1238T>G		intron	N/A	ENSP00000376763.1
	CLTC	ENST00000700714.2		c.2292+1238T>G		intron	N/A	ENSP00000515154.2

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

African (AFR) AF: 0.0609 AC: 2532 AN: 41566

American (AMR) AF: 0.139 AC: 2128 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 417 AN: 3472

East Asian (EAS) AF: 0.454 AC: 2348 AN: 5174

South Asian (SAS) AF: 0.378 AC: 1819 AN: 4816

European-Finnish (FIN) AF: 0.129 AC: 1361 AN: 10580

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0968 AC: 6580 AN: 67984

Other (OTH) AF: 0.124 AC: 262 AN: 2116

Alfa AF: 0.102 Hom.: 1728

Bravo AF: 0.108

Asia WGS AF: 0.400 AC: 1391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.52
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

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: rs10515171; hg19: chr17-57747539;