22-19183540-C-T

Variant names:

• chr22-19183540-C-T
• rs200009376
• NM_007098.4:c.4677G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_007098.4(CLTCL1):​c.4677G>A​(p.Glu1559Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,470 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CLTCL1 NM_007098.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=0.276 with no splicing effect.

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.4677G>A	p.Glu1559Glu	synonymous	Exon 30 of 33	NP_009029.3	P53675-1
	CLTCL1	NM_001835.4		c.4506G>A	p.Glu1502Glu	synonymous	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.4677G>A	p.Glu1559Glu	synonymous	Exon 30 of 33	ENSP00000441158.1	P53675-1
	CLTCL1	ENST00000621271.4	TSL:1	c.4506G>A	p.Glu1502Glu	synonymous	Exon 29 of 32	ENSP00000485020.1	P53675-2
	CLTCL1	ENST00000615606.4	TSL:1	n.4770G>A		non_coding_transcript_exon	Exon 29 of 30

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461470 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727016

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111862

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	2.7
DANN	Benign	0.81
PhyloP100		0.28

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: rs200009376; hg19: chr22-19171053;