rs7224631

chr17-59655553-G-A

Variant summary

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

The NM_004859.4(CLTC):c.796-301G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,114 control chromosomes in the GnomAD database, including 3,371 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 0.18 (3371 hom., cov: 33)
• Consequence: CLTC NM_004859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259

Genes affected

CLTC (HGNC:2092): (clathrin heavy chain) Clathrin is a major protein component of the cytoplasmic face of intracellular organelles, called coated vesicles and coated pits. These specialized organelles are involved in the intracellular trafficking of receptors and endocytosis of a variety of macromolecules. The basic subunit of the clathrin coat is composed of three heavy chains and three light chains. [provided by RefSeq, Jul 2008]

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 (EAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLTC	NM_004859.4	c.796-301G>A		intron_variant		ENST00000269122.8
CLTC	NM_001288653.2	c.808-301G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLTC	ENST00000269122.8	c.796-301G>A		intron_variant		1	NM_004859.4	P4

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27480 AN: 151996 Hom.: 3357 Cov.: 33

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0973

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.181 AC: 27523 AN: 152114 Hom.: 3371 Cov.: 33 AF XY: 0.186 AC XY: 13814 AN XY: 74358

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.0973

Gnomad4 OTH AF: 0.169

Alfa AF: 0.135 Hom.: 900

Bravo AF: 0.182

Asia WGS AF: 0.420 AC: 1462 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	4.1
Dann	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7224631; hg19: chr17-57732914;