rs5746685

chr22-19205086-C-Gchr22-19205086-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLTCL1	NM_007098.4	c.3600+3068G>C		intron_variant		ENST00000427926.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLTCL1	ENST00000427926.6	c.3600+3068G>C		intron_variant		1	NM_007098.4	P1

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

Gnomad4 AFR AF: 0.848

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.594

Gnomad4 EAS AF: 0.829

Gnomad4 SAS AF: 0.767

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.632

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	4.6
Dann	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs5746685; hg19: chr22-19192596;