Genetic Variant NM_002211.4:c.2331+99T>G (chr10-32908269-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002211.4(ITGB1):c.2331+99T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,154,740 control chromosomes in the GnomAD database, including 8,218 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 0.090 ( 890 hom., cov: 32)

Exomes 𝑓: 0.11 ( 7328 hom. )

Consequence

ITGB1
NM_002211.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0980

Publications

16 publications found

Variant links:

Genes affected

ITGB1 (HGNC:6153): (integrin subunit beta 1) Integrins are heterodimeric proteins made up of alpha and beta subunits. At least 18 alpha and 8 beta subunits have been described in mammals. Integrin family members are membrane receptors involved in cell adhesion and recognition in a variety of processes including embryogenesis, hemostasis, tissue repair, immune response and metastatic diffusion of tumor cells. This gene encodes a beta subunit. Multiple alternatively spliced transcript variants which encode different protein isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ITGB1 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=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ITGB1	NM_002211.4 link	c.2331+99T>G	intron_variant	Intron 15 of 15	ENST00000302278.8	NP_002202.2	P05556-1
ITGB1	NM_033668.2 link	c.2331+99T>G	intron_variant	Intron 14 of 15		NP_391988.1	P05556-5
ITGB1	NM_133376.3 link	c.2331+99T>G	intron_variant	Intron 15 of 15		NP_596867.1	P05556-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB1	ENST00000302278.8 link	c.2331+99T>G		intron_variant	Intron 15 of 15	1	NM_002211.4	ENSP00000303351.3		P05556-1

Frequencies

GnomAD3 genomes

AF:

0.0906

AC:

13787

AN:

152144

Hom.:

896

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0310

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0874

Gnomad ASJ

AF:

0.0904

Gnomad EAS

AF:

0.328

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.122

Gnomad MID

AF:

0.121

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.0948

GnomAD4 exome

AF:

0.111

AC:

111472

AN:

1002478

Hom.:

7328

AF XY:

0.113

AC XY:

57980

AN XY:

515362

show subpopulations

African (AFR)

AF:

0.0274

AC:

656

AN:

23916

American (AMR)

AF:

0.0794

AC:

3162

AN:

39828

Ashkenazi Jewish (ASJ)

AF:

0.0933

AC:

2078

AN:

22282

East Asian (EAS)

AF:

0.310

AC:

11597

AN:

37372

South Asian (SAS)

AF:

0.129

AC:

9300

AN:

72364

European-Finnish (FIN)

AF:

0.125

AC:

6538

AN:

52178

Middle Eastern (MID)

AF:

0.123

AC:

579

AN:

4718

European-Non Finnish (NFE)

AF:

0.103

AC:

72756

AN:

704998

Other (OTH)

AF:

0.107

AC:

4806

AN:

44822

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

4863

9726

14589

19452

24315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2188

4376

6564

8752

10940

<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:

0.0904

AC:

13765

AN:

152262

Hom.:

890

Cov.:

AF XY:

0.0931

AC XY:

6934

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0309

AC:

1283

AN:

41572

American (AMR)

AF:

0.0870

AC:

1331

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0904

AC:

314

AN:

3472

East Asian (EAS)

AF:

0.327

AC:

1693

AN:

5180

South Asian (SAS)

AF:

0.134

AC:

646

AN:

4822

European-Finnish (FIN)

AF:

0.122

AC:

1290

AN:

10600

Middle Eastern (MID)

AF:

0.123

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.102

AC:

6937

AN:

68010

Other (OTH)

AF:

0.0934

AC:

197

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

613

1226

1839

2452

3065

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

166

332

498

664

830

<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:

0.0954

Hom.:

982

Bravo

AF:

0.0850

Asia WGS

AF:

0.166

AC:

577

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.3

(source)

DANN

Benign

0.73

PhyloP100

0.098

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