dbSNP rs1375493: ITGA4:c.319+722G>A (chr2-181459039-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000885.6(ITGA4):c.319+722G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 152,070 control chromosomes in the GnomAD database, including 23,926 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 0.56 ( 23919 hom., cov: 32)

Exomes 𝑓: 0.44 ( 7 hom. )

Consequence

ITGA4
NM_000885.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.43

Publications

17 publications found

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 was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000885.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA4	NM_000885.6	MANE Select	c.319+722G>A		intron	N/A	NP_000876.3	P13612-1
	ITGA4	NM_001316312.2		c.319+722G>A		intron	N/A	NP_001303241.1	P13612-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ITGA4	ENST00000397033.7	TSL:1 MANE Select	c.319+722G>A	intron	N/A	ENSP00000380227.2	P13612-1
ITGA4	ENST00000233573.6	TSL:1	c.319+722G>A	intron	N/A	ENSP00000233573.6	E7EP60
ITGA4	ENST00000339307.8	TSL:1	c.319+722G>A	intron	N/A	ENSP00000340149.4	P13612-2

Frequencies

GnomAD3 genomes

AF:

0.557

AC:

84537

AN:

151886

Hom.:

23901

Cov.:

show subpopulations

Gnomad AFR

AF:

0.582

Gnomad AMI

AF:

0.576

Gnomad AMR

AF:

0.538

Gnomad ASJ

AF:

0.490

Gnomad EAS

AF:

0.361

Gnomad SAS

AF:

0.598

Gnomad FIN

AF:

0.633

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.549

Gnomad OTH

AF:

0.545

GnomAD4 exome

AF:

0.439

AC:

AN:

Hom.:

Cov.:

AF XY:

0.464

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.250

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.448

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.557

AC:

84597

AN:

152004

Hom.:

23919

Cov.:

AF XY:

0.560

AC XY:

41632

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.582

AC:

24122

AN:

41440

American (AMR)

AF:

0.538

AC:

8223

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.490

AC:

1696

AN:

3462

East Asian (EAS)

AF:

0.362

AC:

1873

AN:

5178

South Asian (SAS)

AF:

0.598

AC:

2877

AN:

4814

European-Finnish (FIN)

AF:

0.633

AC:

6688

AN:

10564

Middle Eastern (MID)

AF:

0.493

AC:

144

AN:

292

European-Non Finnish (NFE)

AF:

0.549

AC:

37317

AN:

67956

Other (OTH)

AF:

0.539

AC:

1136

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1934

3869

5803

7738

9672

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

722

1444

2166

2888

3610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.547

Hom.:

33263

Bravo

AF:

0.550

Asia WGS

AF:

0.482

AC:

1678

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.54

PhyloP100

2.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over