dbSNP rs12988934: ITGA4:c.319+621C>T (chr2-181458938-C-T) – 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+621C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0636 in 152,368 control chromosomes in the GnomAD database, including 640 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 0.064 ( 640 hom., cov: 32)

Exomes 𝑓: 0.037 ( 0 hom. )

Consequence

ITGA4
NM_000885.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.111

Publications

16 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:

Genome browser will be placed here

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 (EAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA4	NM_000885.6 link	c.319+621C>T		intron_variant	Intron 2 of 27	ENST00000397033.7	NP_000876.3
ITGA4	NM_001316312.2 link	c.319+621C>T		intron_variant	Intron 2 of 4		NP_001303241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA4	ENST00000397033.7 link	c.319+621C>T		intron_variant	Intron 2 of 27	1	NM_000885.6	ENSP00000380227.2

Frequencies

GnomAD3 genomes

AF:

0.0637

AC:

9692

AN:

152114

Hom.:

641

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0122

Gnomad AMI

AF:

0.0495

Gnomad AMR

AF:

0.0387

Gnomad ASJ

AF:

0.0706

Gnomad EAS

AF:

0.282

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.140

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0624

Gnomad OTH

AF:

0.0570

GnomAD4 exome

AF:

0.0368

AC:

AN:

136

Hom.:

Cov.:

AF XY:

0.0385

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.0500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.125

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0189

AC:

AN:

106

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

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:

0.0637

AC:

9690

AN:

152232

Hom.:

640

Cov.:

AF XY:

0.0703

AC XY:

5229

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0122

AC:

507

AN:

41552

American (AMR)

AF:

0.0387

AC:

592

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0706

AC:

245

AN:

3470

East Asian (EAS)

AF:

0.283

AC:

1463

AN:

5172

South Asian (SAS)

AF:

0.200

AC:

962

AN:

4822

European-Finnish (FIN)

AF:

0.140

AC:

1480

AN:

10584

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0624

AC:

4247

AN:

68016

Other (OTH)

AF:

0.0583

AC:

123

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

429

857

1286

1714

2143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

256

384

512

640

<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:

0.0650

Hom.:

1618

Bravo

AF:

0.0517

Asia WGS

AF:

0.221

AC:

769

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.6

(source)

DANN

Benign

0.78

PhyloP100

0.11

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over