Variant 2-181537269-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000885.6(ITGA4):c.*1742G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00815 in 453,592 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.019 ( 74 hom., cov: 33)

Exomes 𝑓: 0.0029 ( 23 hom. )

Consequence

ITGA4
NM_000885.6 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.517

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA4	NM_000885.6 linkuse as main transcript	c.*1742G>C		3_prime_UTR_variant	28/28	ENST00000397033.7
CERKL	NM_201548.5 linkuse as main transcript	c.*915C>G		3_prime_UTR_variant	13/13	ENST00000410087.8

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA4	ENST00000397033.7 linkuse as main transcript	c.*1742G>C	3_prime_UTR_variant	28/28	1	NM_000885.6	P1	P13612-1
CERKL	ENST00000410087.8 linkuse as main transcript	c.*915C>G	3_prime_UTR_variant	13/13	1	NM_201548.5	P1	Q49MI3-2
CERKL	ENST00000684145.1 linkuse as main transcript	c.*915C>G	3_prime_UTR_variant	12/12

Frequencies

GnomAD3 genomes

AF:

0.0185

AC:

2817

AN:

151940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0637

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00578

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000677

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.00447

AC:

572

AN:

127846

Hom.:

AF XY:

0.00384

AC XY:

269

AN XY:

70028

show subpopulations

Gnomad AFR exome

AF:

0.0685

Gnomad AMR exome

AF:

0.00333

Gnomad ASJ exome

AF:

0.00185

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000223

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.000846

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00292

AC:

879

AN:

301534

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

419

AN XY:

171842

show subpopulations

Gnomad4 AFR exome

AF:

0.0654

Gnomad4 AMR exome

AF:

0.00356

Gnomad4 ASJ exome

AF:

0.00213

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000218

Gnomad4 FIN exome

AF:

0.0000809

Gnomad4 NFE exome

AF:

0.000649

Gnomad4 OTH exome

AF:

0.00477

GnomAD4 genome

AF:

0.0185

AC:

2820

AN:

152058

Hom.:

Cov.:

AF XY:

0.0178

AC XY:

1320

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0636

Gnomad4 AMR

AF:

0.00577

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000677

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0119

Hom.:

Bravo

AF:

0.0218

Asia WGS

AF:

0.00347

AC:

AN:

3476

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

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.68

DANN

Benign

0.28

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