Genetic Variant ITGB8:p.Arg57Met (chr7-20363679-G-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002214.3(ITGB8):c.170G>T(p.Arg57Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000519 in 1,605,412 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00054 ( 6 hom. )

Consequence

ITGB8
NM_002214.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.233

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017897367).

BS2

High AC in GnomAd4 at 43 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB8	NM_002214.3 link	c.170G>T	p.Arg57Met	missense_variant	Exon 2 of 14	ENST00000222573.5	NP_002205.1	P26012-1Q9BUG9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ITGB8	ENST00000222573.5 link	c.170G>T	p.Arg57Met	missense_variant	Exon 2 of 14	1	NM_002214.3	ENSP00000222573.3	P26012-1
ITGB8	ENST00000478974.1 link	n.875G>T		non_coding_transcript_exon_variant	Exon 2 of 9	1
ITGB8	ENST00000537992 link	c.-236G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 3 of 15	2		ENSP00000441561.1	P26012-2
ITGB8	ENST00000537992 link	c.-236G>T		5_prime_UTR_variant	Exon 3 of 15	2		ENSP00000441561.1	P26012-2

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00849

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00105

AC:

253

AN:

241786

Hom.:

AF XY:

0.00151

AC XY:

198

AN XY:

131046

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00874

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000681

GnomAD4 exome

AF:

0.000544

AC:

790

AN:

1453196

Hom.:

Cov.:

AF XY:

0.000806

AC XY:

583

AN XY:

722972

show subpopulations

Gnomad4 AFR exome

AF:

0.0000909

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00898

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.000500

GnomAD4 genome

AF:

0.000282

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00870

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000501

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.00126

AC:

153

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Uncertain

0.67

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.48

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.52

MutationAssessor

Benign

0.90

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.7

REVEL

Uncertain

0.36

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.013

Polyphen

0.56

Vest4

0.34

MutPred

0.61

Loss of loop (P = 0.1242);

MVP

0.55

MPC

0.16

ClinPred

0.072

GERP RS

-3.1

Varity_R

0.11

gMVP

0.52

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over