Genetic Variant NM_002214.3:c.127+202G>A (chr7-20332135-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_002214.3(ITGB8):c.127+202G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,154,244 control chromosomes in the GnomAD database, including 119,613 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 0.52 ( 21936 hom., cov: 33)

Exomes 𝑓: 0.43 ( 97677 hom. )

Consequence

ITGB8
NM_002214.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.270

Publications

4 publications found

Variant links:

Genes affected

ITGB8 (HGNC:6163): (integrin subunit beta 8) This gene is a member of the integrin beta chain family and encodes a single-pass type I membrane protein with a VWFA domain and four cysteine-rich repeats. This protein noncovalently binds to an alpha subunit to form a heterodimeric integrin complex. In general, integrin complexes mediate cell-cell and cell-extracellular matrix interactions and this complex plays a role in human airway epithelial proliferation. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

ITGB8 links:

ITGB8-AS1 (HGNC:55257): (ITGB8 antisense RNA 1)

ITGB8-AS1 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=-0.79).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002214.3. 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
	ITGB8	NM_002214.3	MANE Select	c.127+202G>A		intron	N/A	NP_002205.1	P26012-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ITGB8	ENST00000222573.5	TSL:1 MANE Select	c.127+202G>A	intron	N/A	ENSP00000222573.3	P26012-1
ITGB8	ENST00000460204.1	TSL:1	n.47+112G>A	intron	N/A
ITGB8	ENST00000478974.1	TSL:1	n.832+202G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.517

AC:

78566

AN:

151968

Hom.:

21909

Cov.:

show subpopulations

Gnomad AFR

AF:

0.710

Gnomad AMI

AF:

0.357

Gnomad AMR

AF:

0.585

Gnomad ASJ

AF:

0.382

Gnomad EAS

AF:

0.633

Gnomad SAS

AF:

0.646

Gnomad FIN

AF:

0.384

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.397

Gnomad OTH

AF:

0.494

GnomAD4 exome

AF:

0.431

AC:

432406

AN:

1002158

Hom.:

97677

AF XY:

0.435

AC XY:

214238

AN XY:

492396

show subpopulations

African (AFR)

AF:

0.716

AC:

16245

AN:

22674

American (AMR)

AF:

0.630

AC:

11502

AN:

18254

Ashkenazi Jewish (ASJ)

AF:

0.401

AC:

6541

AN:

16310

East Asian (EAS)

AF:

0.642

AC:

20750

AN:

32334

South Asian (SAS)

AF:

0.631

AC:

31535

AN:

49952

European-Finnish (FIN)

AF:

0.370

AC:

10349

AN:

28006

Middle Eastern (MID)

AF:

0.429

AC:

1272

AN:

2964

European-Non Finnish (NFE)

AF:

0.399

AC:

314246

AN:

787880

Other (OTH)

AF:

0.456

AC:

19966

AN:

43784

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

11149

22299

33448

44598

55747

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9790

19580

29370

39160

48950

<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:

0.517

AC:

78651

AN:

152086

Hom.:

21936

Cov.:

AF XY:

0.520

AC XY:

38655

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.709

AC:

29424

AN:

41478

American (AMR)

AF:

0.585

AC:

8952

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.382

AC:

1324

AN:

3466

East Asian (EAS)

AF:

0.633

AC:

3267

AN:

5162

South Asian (SAS)

AF:

0.645

AC:

3110

AN:

4820

European-Finnish (FIN)

AF:

0.384

AC:

4062

AN:

10580

Middle Eastern (MID)

AF:

0.479

AC:

140

AN:

292

European-Non Finnish (NFE)

AF:

0.397

AC:

27004

AN:

67972

Other (OTH)

AF:

0.494

AC:

1043

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1834

3668

5501

7335

9169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

664

1328

1992

2656

3320

<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:

0.448

Hom.:

21151

Bravo

AF:

0.537

Asia WGS

AF:

0.655

AC:

2281

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.0

(source)

DANN

Benign

0.74

PhyloP100

-0.27

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