22-19183486-AAGCAGGTCAT-A

Position:

• chr22-19183486-AAGCAGGTCAT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_007098.4(CLTCL1):​c.4721_4730del​(p.Tyr1574PhefsTer26) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,613,810 control chromosomes in the GnomAD database, including 16 homozygotes. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0018 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (14 hom.)
• Consequence: CLTCL1 NM_007098.4 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 9.04

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 22-19183486-AAGCAGGTCAT-A is Benign according to our data. Variant chr22-19183486-AAGCAGGTCAT-A is described in ClinVar as [Benign]. Clinvar id is 784888.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00109 (1586/1461460) while in subpopulation AMR AF= 0.0261 (1165/44718). AF 95% confidence interval is 0.0248. There are 14 homozygotes in gnomad4_exome. There are 688 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLTCL1	NM_007098.4	c.4721_4730del	p.Tyr1574PhefsTer26	frameshift_variant	30/33	ENST00000427926.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLTCL1	ENST00000427926.6	c.4721_4730del	p.Tyr1574PhefsTer26	frameshift_variant	30/33	1	NM_007098.4	P1

Frequencies

GnomAD3 genomes AF: 0.00177 AC: 270 AN: 152232 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0139

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00411 AC: 1023 AN: 248878 Hom.: 10 AF XY: 0.00321 AC XY: 434 AN XY: 135098

Gnomad AFR exome AF: 0.000323

Gnomad AMR exome AF: 0.0266

Gnomad ASJ exome AF: 0.00538

Gnomad EAS exome AF: 0.00134

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000887

Gnomad OTH exome AF: 0.00182

GnomAD4 exome AF: 0.00109 AC: 1586 AN: 1461460 Hom.: 14 AF XY: 0.000946 AC XY: 688 AN XY: 727010

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.0261

Gnomad4 ASJ exome AF: 0.00536

Gnomad4 EAS exome AF: 0.00327

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000432

Gnomad4 OTH exome AF: 0.00142

GnomAD4 genome AF: 0.00179 AC: 272 AN: 152350 Hom.: 2 Cov.: 33 AF XY: 0.00146 AC XY: 109 AN XY: 74492

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.0140

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00178 Hom.: 0

Bravo AF: 0.00332

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs563734046; hg19: chr22-19170999;