rs5746685

Variant names:

• chr22-19205086-C-G
• rs5746685
• NM_007098.4:c.3600+3068G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-19205086-C-G
• chr22-19205086-C-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.3600+3068G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 151,222 control chromosomes in the GnomAD database, including 35,778 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 0.68 (35778 hom., cov: 31)
• Consequence: CLTCL1 NM_007098.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

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.3600+3068G>C		intron	N/A	NP_009029.3	P53675-1
	CLTCL1	NM_001835.4		c.3600+3068G>C		intron	N/A	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.3600+3068G>C		intron	N/A	ENSP00000441158.1	P53675-1
	CLTCL1	ENST00000621271.4	TSL:1	c.3600+3068G>C		intron	N/A	ENSP00000485020.1	P53675-2
	CLTCL1	ENST00000615606.4	TSL:1	n.3620+3068G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.676 AC: 102072 AN: 151104 Hom.: 35734 Cov.: 31

Gnomad AFR AF: 0.848

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.676 AC: 102177 AN: 151222 Hom.: 35778 Cov.: 31 AF XY: 0.681 AC XY: 50219 AN XY: 73796

African (AFR) AF: 0.848 AC: 34968 AN: 41234

American (AMR) AF: 0.660 AC: 10045 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2059 AN: 3466

East Asian (EAS) AF: 0.829 AC: 4244 AN: 5118

South Asian (SAS) AF: 0.767 AC: 3665 AN: 4780

European-Finnish (FIN) AF: 0.624 AC: 6440 AN: 10318

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.571 AC: 38692 AN: 67784

Other (OTH) AF: 0.632 AC: 1324 AN: 2094

Alfa AF: 0.520 Hom.: 1638

Bravo AF: 0.680

Asia WGS AF: 0.793 AC: 2757 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.6
DANN	Benign	0.70
PhyloP100		-0.083
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: rs5746685; hg19: chr22-19192596;