rs1206549

Variant names:

• chr22-19228337-G-A
• rs1206549
• NM_007098.4:c.1782+1501C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007098.4(CLTCL1):​c.1782+1501C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,100 control chromosomes in the GnomAD database, including 5,000 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 0.23 (5000 hom., cov: 32)
• Consequence: CLTCL1 NM_007098.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.679
• Publications: 3 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]

CLTCL1 Gene-Disease associations (from GenCC):

• congenital insensitivity to pain with severe intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLTCL1	NM_007098.4	c.1782+1501C>T		intron_variant	Intron 11 of 32	ENST00000427926.6	NP_009029.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLTCL1	ENST00000427926.6	c.1782+1501C>T		intron_variant	Intron 11 of 32	1	NM_007098.4	ENSP00000441158.1
CLTCL1	ENST00000621271.4	c.1782+1501C>T		intron_variant	Intron 11 of 31	1		ENSP00000485020.1
CLTCL1	ENST00000615606.4	n.1802+1501C>T		intron_variant	Intron 11 of 29	1
CLTCL1	ENST00000617103.4	n.1782+1501C>T		intron_variant	Intron 11 of 30	1		ENSP00000480709.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35302 AN: 151982 Hom.: 4985 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.224

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.232 AC: 35356 AN: 152100 Hom.: 5000 Cov.: 32 AF XY: 0.233 AC XY: 17299 AN XY: 74362

African (AFR) AF: 0.392 AC: 16232 AN: 41456

American (AMR) AF: 0.240 AC: 3676 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 420 AN: 3468

East Asian (EAS) AF: 0.261 AC: 1347 AN: 5170

South Asian (SAS) AF: 0.209 AC: 1011 AN: 4832

European-Finnish (FIN) AF: 0.146 AC: 1543 AN: 10582

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10496 AN: 67982

Other (OTH) AF: 0.222 AC: 469 AN: 2114

Alfa AF: 0.189 Hom.: 1186

Bravo AF: 0.245

Asia WGS AF: 0.240 AC: 838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.4
DANN	Benign	0.35
PhyloP100		-0.68
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: rs1206549; hg19: chr22-19215860;