Variant 2-181536766-A-ACAAT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000885.6(ITGA4):c.*1242_*1245dupATCA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 248,654 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

ITGA4
NM_000885.6 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.85

Variant links:

Genes affected

ITGA4 (HGNC:6140): (integrin subunit alpha 4) The gene encodes a member of the integrin alpha chain family of proteins. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha 4 subunit. This subunit associates with a beta 1 or beta 7 subunit to form an integrin that may play a role in cell motility and migration. This integrin is a therapeutic target for the treatment of multiple sclerosis, Crohn's disease and inflammatory bowel disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

ITGA4 links:

CERKL (HGNC:21699): (ceramide kinase like) This gene was initially identified as a locus (RP26) associated with an autosomal recessive form of retinitis pigmentosa (arRP) disease. This gene encodes a protein with ceramide kinase-like domains, however, the protein does not phosphorylate ceramide and its target substrate is currently unknown. This protein may be a negative regulator of apoptosis in photoreceptor cells. Mutations in this gene cause a form of retinitis pigmentosa characterized by autosomal recessive cone and rod dystrophy (arCRD). Alternative splicing of this gene results in multiple transcript variants encoding different isoforms and non-coding transcripts.[provided by RefSeq, May 2010]

CERKL links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 342 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA4	NM_000885.6 link	c.1242_1245dupATCA		3_prime_UTR_variant	28/28	ENST00000397033.7	NP_000876.3	P13612-1
CERKL	NM_201548.5 link	c.1414_1417dupATTG		3_prime_UTR_variant	13/13	ENST00000410087.8	NP_963842.1	Q49MI3-2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ITGA4	ENST00000397033.7 link	c.1242_1245dupATCA	3_prime_UTR_variant	28/28	1	NM_000885.6	ENSP00000380227.2	P13612-1
CERKL	ENST00000410087 link	c.1414_1417dupATTG	3_prime_UTR_variant	13/13	1	NM_201548.5	ENSP00000386725.3	Q49MI3-2
CERKL	ENST00000684145 link	c.1414_1417dupATTG	3_prime_UTR_variant	12/12			ENSP00000508396.1	G0XYE7

Frequencies

GnomAD3 genomes

AF:

0.00223

AC:

339

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00775

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000525

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000890

AC:

AN:

25830

Hom.:

AF XY:

0.000585

AC XY:

AN XY:

13682

show subpopulations

Gnomad AFR exome

AF:

0.00623

Gnomad AMR exome

AF:

0.000270

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00194

Gnomad SAS exome

AF:

0.000317

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000342

AC:

AN:

96458

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

AN XY:

52220

show subpopulations

Gnomad4 AFR exome

AF:

0.00709

Gnomad4 AMR exome

AF:

0.000222

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00178

Gnomad4 SAS exome

AF:

0.000175

Gnomad4 FIN exome

AF:

0.000199

Gnomad4 NFE exome

AF:

0.0000539

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.00225

AC:

342

AN:

152196

Hom.:

Cov.:

AF XY:

0.00231

AC XY:

172

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00780

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00230

Hom.:

Bravo

AF:

0.00260

Asia WGS

AF:

0.000289

AC:

AN:

3472

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Retinitis Pigmentosa, Recessive

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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