rs885978

chr22-19210716-A-Gchr22-19210716-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007098.4(CLTCL1):c.3066-207T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 152,060 control chromosomes in the GnomAD database, including 36,887 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 (36887 hom., cov: 31)
• Consequence: CLTCL1 NM_007098.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.637

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLTCL1	NM_007098.4	c.3066-207T>C		intron_variant		ENST00000427926.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLTCL1	ENST00000427926.6	c.3066-207T>C		intron_variant		1	NM_007098.4	P1
CLTCL1	ENST00000621271.4	c.3066-207T>C		intron_variant		1
CLTCL1	ENST00000617103.4	c.3066-207T>C		intron_variant, NMD_transcript_variant		1
CLTCL1	ENST00000615606.4	n.3086-207T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103649 AN: 151942 Hom.: 36832 Cov.: 31

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.762

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.682 AC: 103767 AN: 152060 Hom.: 36887 Cov.: 31 AF XY: 0.687 AC XY: 51024 AN XY: 74308

Gnomad4 AFR AF: 0.871

Gnomad4 AMR AF: 0.662

Gnomad4 ASJ AF: 0.594

Gnomad4 EAS AF: 0.824

Gnomad4 SAS AF: 0.762

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.639

Alfa AF: 0.592 Hom.: 11344

Bravo AF: 0.688

Asia WGS AF: 0.798 AC: 2777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	2.2
Dann	Benign	0.76

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: rs885978; hg19: chr22-19198226;