9-36198973-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001833.4(CLTA):c.256-6G>A variant causes a splice region, splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.00548 in 1,600,302 control chromosomes in the GnomAD database, including 444 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.028 (220 hom., cov: 31)
  • Exomes 𝑓: 0.0031 (224 hom.)
• Consequence: CLTA NM_001833.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.01433
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.06

Genes affected

CLTA (HGNC:2090): (clathrin light chain A) Clathrin is a large, soluble protein composed of heavy and light chains. It functions as the main structural component of the lattice-type cytoplasmic face of coated pits and vesicles which entrap specific macromolecules during receptor-mediated endocytosis. This gene encodes one of two clathrin light chain proteins which are believed to function as regulatory elements. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 8 and 12. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 9-36198973-G-A is Benign according to our data. Variant chr9-36198973-G-A is described in ClinVar as [Benign]. Clinvar id is 792127.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLTA	NM_001833.4	c.256-6G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000345519.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLTA	ENST00000345519.10	c.256-6G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001833.4	A1

Frequencies

GnomAD3 genomes AF: 0.0285 AC: 4329 AN: 151976 Hom.: 220 Cov.: 31

Gnomad AFR AF: 0.0994

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00969

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000324

Gnomad OTH AF: 0.0215

GnomAD3 exomes AF: 0.00748 AC: 1882 AN: 251444 Hom.: 84 AF XY: 0.00535 AC XY: 727 AN XY: 135896

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.00422

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000359

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000334

Gnomad OTH exome AF: 0.00505

GnomAD4 exome AF: 0.00307 AC: 4444 AN: 1448214 Hom.: 224 Cov.: 28 AF XY: 0.00264 AC XY: 1907 AN XY: 721392

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.00493

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000500

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000215

Gnomad4 OTH exome AF: 0.00649

GnomAD4 genome AF: 0.0285 AC: 4332 AN: 152088 Hom.: 220 Cov.: 31 AF XY: 0.0275 AC XY: 2043 AN XY: 74362

Gnomad4 AFR AF: 0.0992

Gnomad4 AMR AF: 0.00968

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.0000946

Gnomad4 NFE AF: 0.000324

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0142 Hom.: 29

Bravo AF: 0.0324

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
Cadd	Benign	14
Dann	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.014
dbscSNV1_RF	Benign	0.078
SpliceAI score (max)		0.050		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: rs79205619; hg19: chr9-36198970;