9-36193491-G-T

Variant names:

• chr9-36193491-G-T
• rs10972786
• NM_001833.4:c.217+2218G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001833.4(CLTA):​c.217+2218G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0944 in 151,982 control chromosomes in the GnomAD database, including 917 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 0.094 (917 hom., cov: 32)
• Consequence: CLTA NM_001833.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001833.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLTA	NM_001833.4	MANE Select	c.217+2218G>T		intron	N/A	NP_001824.1
	CLTA	NM_007096.4		c.217+2218G>T		intron	N/A	NP_009027.1
	CLTA	NM_001076677.3		c.217+2218G>T		intron	N/A	NP_001070145.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLTA	ENST00000345519.10	TSL:1 MANE Select	c.217+2218G>T		intron	N/A	ENSP00000242284.6
	CLTA	ENST00000242285.11	TSL:1	c.217+2218G>T		intron	N/A	ENSP00000242285.6
	CLTA	ENST00000396603.6	TSL:1	c.217+2218G>T		intron	N/A	ENSP00000379848.2

Frequencies

GnomAD3 genomes AF: 0.0944 AC: 14336 AN: 151864 Hom.: 916 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0839

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.0182

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.0575

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.0944 AC: 14353 AN: 151982 Hom.: 917 Cov.: 32 AF XY: 0.0949 AC XY: 7051 AN XY: 74290

African (AFR) AF: 0.153 AC: 6342 AN: 41418

American (AMR) AF: 0.0840 AC: 1282 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 563 AN: 3470

East Asian (EAS) AF: 0.170 AC: 876 AN: 5158

South Asian (SAS) AF: 0.176 AC: 847 AN: 4818

European-Finnish (FIN) AF: 0.0182 AC: 192 AN: 10554

Middle Eastern (MID) AF: 0.127 AC: 37 AN: 292

European-Non Finnish (NFE) AF: 0.0575 AC: 3909 AN: 67984

Other (OTH) AF: 0.113 AC: 239 AN: 2114

Alfa AF: 0.0657 Hom.: 280

Bravo AF: 0.0996

Asia WGS AF: 0.176 AC: 611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.69
PhyloP100		-0.25
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: rs10972786; hg19: chr9-36193488;