Genetic Variant ITGB6:p.Gly757Gly (chr2-160101832-T-C) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000888.5(ITGB6):c.2271A>G(p.Gly757Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000218 in 1,399,780 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

ITGB6
NM_000888.5 splice_region, synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.05

Publications

1 publications found

Variant links:

Genes affected

ITGB6 (HGNC:6161): (integrin subunit beta 6) This gene encodes a protein that is a member of the integrin superfamily. Members of this family are adhesion receptors that function in signaling from the extracellular matrix to the cell. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. The encoded protein forms a dimer with an alpha v chain and this heterodimer can bind to ligands like fibronectin and transforming growth factor beta 1. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ITGB6 Gene-Disease associations (from GenCC):

amelogenesis imperfecta type 1H
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
amelogenesis imperfecta type 1
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
amelogenesis imperfecta, type 3A
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ITGB6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 2-160101832-T-C is Benign according to our data. Variant chr2-160101832-T-C is described in ClinVar as Benign. ClinVar VariationId is 736909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0817 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000888.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITGB6	NM_000888.5	MANE Select	c.2271A>G	p.Gly757Gly	splice_region synonymous	Exon 15 of 15	NP_000879.2
ITGB6	NM_001282353.2		c.2271A>G	p.Gly757Gly	splice_region synonymous	Exon 16 of 16	NP_001269282.1	P18564-1
ITGB6	NM_001282388.2		c.2145A>G	p.Gly715Gly	splice_region synonymous	Exon 14 of 14	NP_001269317.1	E9PEE8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITGB6	ENST00000283249.7	TSL:1 MANE Select	c.2271A>G	p.Gly757Gly	splice_region synonymous	Exon 15 of 15	ENSP00000283249.2	P18564-1
ITGB6	ENST00000409872.1	TSL:1	c.2271A>G	p.Gly757Gly	splice_region synonymous	Exon 16 of 16	ENSP00000386367.1	P18564-1
ITGB6	ENST00000958494.1		c.2358A>G	p.Gly786Gly	splice_region synonymous	Exon 16 of 16	ENSP00000628553.1

Frequencies

GnomAD3 genomes

AF:

0.00522

AC:

AN:

9962

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.106

Gnomad SAS

AF:

0.0149

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00980

GnomAD2 exomes

AF:

0.000985

AC:

142

AN:

144132

AF XY:

0.000861

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0168

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000730

GnomAD4 exome

AF:

0.000183

AC:

254

AN:

1389772

Hom.:

Cov.:

AF XY:

0.000153

AC XY:

106

AN XY:

694732

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31338

American (AMR)

AF:

0.0000723

AC:

AN:

41510

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25544

East Asian (EAS)

AF:

0.00527

AC:

207

AN:

39296

South Asian (SAS)

AF:

0.000185

AC:

AN:

81256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53206

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5608

European-Non Finnish (NFE)

AF:

9.49e-7

AC:

AN:

1054094

Other (OTH)

AF:

0.000483

AC:

AN:

57920

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.00510

AC:

AN:

10008

Hom.:

Cov.:

AF XY:

0.00655

AC XY:

AN XY:

4888

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

2458

American (AMR)

AF:

0.00

AC:

AN:

568

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

276

East Asian (EAS)

AF:

0.106

AC:

AN:

434

South Asian (SAS)

AF:

0.0116

AC:

AN:

346

European-Finnish (FIN)

AF:

0.00

AC:

AN:

612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

5052

Other (OTH)

AF:

0.00893

AC:

AN:

112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.0000306

Hom.:

Bravo

AF:

0.000355

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

2.1

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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