chr22-19183561-C-CT

Variant names:

• chr22-19183561-C-CT
• rs375471950
• NM_007098.4:c.4655dupA

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_007098.4(CLTCL1):​c.4655dupA​(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
• Publications: 0 publications found

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]

LINC01311 (HGNC:50503): (long intergenic non-protein coding RNA 1311)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• 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 VariationId is 718483.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007098.4. 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
	CLTCL1	NM_007098.4	MANE Select	c.4655dupA	p.Leu1553ValfsTer23	frameshift	Exon 30 of 33	NP_009029.3	P53675-1
	CLTCL1	NM_001835.4		c.4484dupA	p.Leu1496ValfsTer23	frameshift	Exon 29 of 32	NP_001826.3	P53675-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLTCL1	ENST00000427926.6	TSL:1 MANE Select	c.4655dupA	p.Leu1553ValfsTer23	frameshift	Exon 30 of 33	ENSP00000441158.1	P53675-1
	CLTCL1	ENST00000621271.4	TSL:1	c.4484dupA	p.Leu1496ValfsTer23	frameshift	Exon 29 of 32	ENSP00000485020.1	P53675-2
	CLTCL1	ENST00000615606.4	TSL:1	n.4748dupA		non_coding_transcript_exon	Exon 29 of 30

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

GnomAD2 exomes AF: 0.000518 AC: 129 AN: 249010 AF XY: 0.000437

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 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

African (AFR) AF: 0.000358 AC: 12 AN: 33480

American (AMR) AF: 0.000939 AC: 42 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00222 AC: 58 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53166

Middle Eastern (MID) AF: 0.00330 AC: 19 AN: 5766

European-Non Finnish (NFE) AF: 0.000264 AC: 293 AN: 1111862

Other (OTH) AF: 0.000895 AC: 54 AN: 60368

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

African (AFR) AF: 0.000337 AC: 14 AN: 41598

American (AMR) AF: 0.00124 AC: 19 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000367 AC: 25 AN: 68038

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000982 Hom.: 0

Bravo AF: 0.000597

EpiCase AF: 0.000654

EpiControl AF: 0.000948

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0
Mutation Taster		=59/141	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs375471950; hg19: chr22-19171074;