Variant 2-181480276-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000885.6(ITGA4):c.754+10A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 1,358,832 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 23 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 12 hom. )

Consequence

ITGA4
NM_000885.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.23

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 2-181480276-A-C is Benign according to our data. Variant chr2-181480276-A-C is described in ClinVar as [Benign]. Clinvar id is 785982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.011 (1677/152186) while in subpopulation AFR AF= 0.0382 (1585/41542). AF 95% confidence interval is 0.0366. There are 23 homozygotes in gnomad4. There are 777 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1677 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA4	NM_000885.6 link	c.754+10A>C		intron_variant		ENST00000397033.7	NP_000876.3	P13612-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
ITGA4	ENST00000397033.7 link	c.754+10A>C	intron_variant	1	NM_000885.6	ENSP00000380227.2	P13612-1
ITGA4	ENST00000233573.6 link	c.754+10A>C	intron_variant	1		ENSP00000233573.6	E7EP60
ITGA4	ENST00000465522.5 link	n.1005+10A>C	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0110

AC:

1673

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0382

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00426

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000177

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00321

AC:

566

AN:

176084

Hom.:

AF XY:

0.00234

AC XY:

227

AN XY:

96900

show subpopulations

Gnomad AFR exome

AF:

0.0405

Gnomad AMR exome

AF:

0.00245

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000261

Gnomad OTH exome

AF:

0.00134

GnomAD4 exome

AF:

0.00109

AC:

1310

AN:

1206646

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

633

AN XY:

602714

show subpopulations

Gnomad4 AFR exome

AF:

0.0362

Gnomad4 AMR exome

AF:

0.00255

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000336

Gnomad4 FIN exome

AF:

0.0000207

Gnomad4 NFE exome

AF:

0.000162

Gnomad4 OTH exome

AF:

0.00297

GnomAD4 genome

AF:

0.0110

AC:

1677

AN:

152186

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

777

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0382

Gnomad4 AMR

AF:

0.00426

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00822

Hom.:

Bravo

AF:

0.0127

Asia WGS

AF:

0.00289

AC:

AN:

3470

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	Apr 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.80

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

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