chr22-19183561-C-CT

Position:

• chr22-19183561-C-CT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_007098.4(CLTCL1):​c.4655_4656insA​(p.Leu1553ValfsTer23) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000338 in 1,613,828 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00033 (1 hom.)
• Consequence: CLTCL1 NM_007098.4 frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.03

Genes affected

CLTCL1 (HGNC:2093): (clathrin heavy chain like 1) This gene is a member of the clathrin heavy chain family and encodes a major protein of the polyhedral coat of coated pits and vesicles. Chromosomal aberrations involving this gene are associated with meningioma, DiGeorge syndrome, and velo-cardio-facial syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 22-19183561-C-CT is Benign according to our data. Variant chr22-19183561-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 718483.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLTCL1	NM_007098.4	c.4655_4656insA	p.Leu1553ValfsTer23	frameshift_variant	30/33	ENST00000427926.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLTCL1	ENST00000427926.6	c.4655_4656insA	p.Leu1553ValfsTer23	frameshift_variant	30/33	1	NM_007098.4	P1

Frequencies

GnomAD3 genomes AF: 0.000433 AC: 66 AN: 152258 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000518 AC: 129 AN: 249010 Hom.: 0 AF XY: 0.000437 AC XY: 59 AN XY: 135130

Gnomad AFR exome AF: 0.000451

Gnomad AMR exome AF: 0.000956

Gnomad ASJ exome AF: 0.00249

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000497

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.000328 AC: 479 AN: 1461452 Hom.: 1 Cov.: 31 AF XY: 0.000323 AC XY: 235 AN XY: 727008

Gnomad4 AFR exome AF: 0.000358

Gnomad4 AMR exome AF: 0.000939

Gnomad4 ASJ exome AF: 0.00222

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000264

Gnomad4 OTH exome AF: 0.000895

GnomAD4 genome AF: 0.000433 AC: 66 AN: 152376 Hom.: 0 Cov.: 33 AF XY: 0.000483 AC XY: 36 AN XY: 74514

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000367

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000982 Hom.: 0

Bravo AF: 0.000597

EpiCase AF: 0.000654

EpiControl AF: 0.000948

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs375471950; hg19: chr22-19171074;