chr2-181480276-A-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
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
NM_000885.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.23
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 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_single_submitter, 1 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 GnomAd at 1673 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITGA4 | NM_000885.6 | c.754+10A>C | intron_variant | ENST00000397033.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITGA4 | ENST00000397033.7 | c.754+10A>C | intron_variant | 1 | NM_000885.6 | P1 | |||
ITGA4 | ENST00000233573.6 | c.754+10A>C | intron_variant | 1 | |||||
ITGA4 | ENST00000465522.5 | n.1005+10A>C | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0110 AC: 1673AN: 152068Hom.: 23 Cov.: 32
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GnomAD3 exomes AF: 0.00321 AC: 566AN: 176084Hom.: 5 AF XY: 0.00234 AC XY: 227AN XY: 96900
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GnomAD4 exome AF: 0.00109 AC: 1310AN: 1206646Hom.: 12 Cov.: 17 AF XY: 0.00105 AC XY: 633AN XY: 602714
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Apr 16, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at