Variant 9-36198973-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

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, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.06

Variant links:

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]

CLTA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
CLTA	NM_001833.4 linkuse as main transcript	c.256-6G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000345519.10	NP_001824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLTA	ENST00000345519.10 linkuse as main transcript	c.256-6G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001833.4	ENSP00000242284	A1	P09496-2

Frequencies

GnomAD3 genomes

AF:

0.0285

AC:

4329

AN:

151976

Hom.:

220

Cov.:

show subpopulations

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.:

AF XY:

0.00535

AC XY:

727

AN XY:

135896

show subpopulations

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.:

AF XY:

0.00264

AC XY:

1907

AN XY:

721392

show subpopulations

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.:

AF XY:

0.0275

AC XY:

2043

AN XY:

74362

show subpopulations

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.:

Bravo

AF:

0.0324

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over