rs885978

Variant names:

• chr22-19210716-A-G
• rs885978
• NM_007098.4:c.3066-207T>C

Your query was ambiguous. Multiple possible variants found:

• chr22-19210716-A-G
• chr22-19210716-A-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.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
• Publications: 9 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 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.3066-207T>C		intron	N/A	NP_009029.3	P53675-1
	CLTCL1	NM_001835.4		c.3066-207T>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.3066-207T>C		intron	N/A	ENSP00000441158.1	P53675-1
	CLTCL1	ENST00000621271.4	TSL:1	c.3066-207T>C		intron	N/A	ENSP00000485020.1	P53675-2
	CLTCL1	ENST00000615606.4	TSL:1	n.3086-207T>C		intron	N/A

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

African (AFR) AF: 0.871 AC: 36156 AN: 41496

American (AMR) AF: 0.662 AC: 10113 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2057 AN: 3464

East Asian (EAS) AF: 0.824 AC: 4265 AN: 5176

South Asian (SAS) AF: 0.762 AC: 3676 AN: 4824

European-Finnish (FIN) AF: 0.625 AC: 6584 AN: 10532

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.571 AC: 38827 AN: 67988

Other (OTH) AF: 0.639 AC: 1350 AN: 2112

Alfa AF: 0.592 Hom.: 12910

Bravo AF: 0.688

Asia WGS AF: 0.798 AC: 2777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.2
DANN	Benign	0.76
PhyloP100		-0.64
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: rs885978; hg19: chr22-19198226;