Genetic Variant ITGB8:c.127+23_127+27dupGTTTT (chr7-20331938-G-GTTGTT) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The ENST00000222573.5(ITGB8):c.127+5_127+6insTTGTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,614,026 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 2 hom., cov: 34)

Exomes 𝑓: 0.0015 ( 4 hom. )

Consequence

ITGB8
ENST00000222573.5 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.86

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: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 7-20331938-G-GTTGTT is Benign according to our data. Variant chr7-20331938-G-GTTGTT is described in ClinVar as [Benign]. Clinvar id is 2041445.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 358 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB8	NM_002214.3 link	c.127+23_127+27dupGTTTT		intron_variant	Intron 1 of 13	ENST00000222573.5	NP_002205.1	P26012-1Q9BUG9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB8	ENST00000222573.5 link	c.127+5_127+6insTTGTT		splice_region_variant, intron_variant	Intron 1 of 13	1	NM_002214.3	ENSP00000222573.3		P26012-1

Frequencies

GnomAD3 genomes

AF:

0.00236

AC:

359

AN:

152268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000313

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0128

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00154

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00233

AC:

578

AN:

248080

AF XY:

0.00194

show subpopulations

Gnomad AFR exome

AF:

0.000555

Gnomad AMR exome

AF:

0.00934

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.000817

Gnomad FIN exome

AF:

0.000927

Gnomad NFE exome

AF:

0.00169

Gnomad OTH exome

AF:

0.00197

GnomAD4 exome

AF:

0.00154

AC:

2255

AN:

1461640

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

1025

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

AC:

AN:

33454

Gnomad4 AMR exome

AF:

0.00895

AC:

400

AN:

44700

Gnomad4 ASJ exome

AF:

0.000727

AC:

AN:

26136

Gnomad4 EAS exome

AF:

0.000554

AC:

AN:

39696

Gnomad4 SAS exome

AF:

0.0000464

AC:

AN:

86232

Gnomad4 FIN exome

AF:

0.000955

AC:

AN:

53394

Gnomad4 NFE exome

AF:

0.00152

AC:

1689

AN:

1111924

Gnomad4 Remaining exome

AF:

0.000977

AC:

AN:

60382

Heterozygous variant carriers

129

258

387

516

645

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<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:

0.00235

AC:

358

AN:

152386

Hom.:

Cov.:

AF XY:

0.00271

AC XY:

202

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.000313

AC:

0.00031253

AN:

0.00031253

Gnomad4 AMR

AF:

0.0127

AC:

0.0127384

AN:

0.0127384

Gnomad4 ASJ

AF:

0.000865

AC:

0.000864553

AN:

0.000864553

Gnomad4 EAS

AF:

0.000578

AC:

0.000577812

AN:

0.000577812

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00141

AC:

0.0014119

AN:

0.0014119

Gnomad4 NFE

AF:

0.00153

AC:

0.00152847

AN:

0.00152847

Gnomad4 OTH

AF:

0.00284

AC:

0.00283554

AN:

0.00283554

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome 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

Alfa

AF:

0.000473

Hom.:

Bravo

AF:

0.00261

EpiCase

AF:

0.00120

EpiControl

AF:

0.00119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 10, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=95/5

polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over