chr7-20367039-G-A

Variant names:

• chr7-20367039-G-A
• rs1034995435
• NM_002214.3:c.241G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS2

The NM_002214.3(ITGB8):​c.241G>A​(p.Glu81Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000343 in 1,459,306 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ITGB8 NM_002214.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.91

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB8	NM_002214.3	c.241G>A	p.Glu81Lys	missense_variant	Exon 3 of 14	ENST00000222573.5	NP_002205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB8	ENST00000222573.5	c.241G>A	p.Glu81Lys	missense_variant	Exon 3 of 14	1	NM_002214.3	ENSP00000222573.3
ITGB8	ENST00000477859.1	n.2395G>A		non_coding_transcript_exon_variant	Exon 1 of 2	1
ITGB8	ENST00000478974.1	n.946G>A		non_coding_transcript_exon_variant	Exon 3 of 9	1
ITGB8	ENST00000537992	c.-165G>A		5_prime_UTR_variant	Exon 4 of 15	2		ENSP00000441561.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248910 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134356

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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1459306 Hom.: 0 Cov.: 29 AF XY: 0.00000413 AC XY: 3 AN XY: 725732

Gnomad4 AFR exome AF: 0.0000300

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 29, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.241G>A (p.E81K) alteration is located in exon 3 (coding exon 3) of the ITGB8 gene. This alteration results from a G to A substitution at nucleotide position 241, causing the glutamic acid (E) at amino acid position 81 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T
Eigen	Benign	-0.057
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.072	D
MetaRNN	Uncertain	0.50	D
MetaSVM	Uncertain	-0.043	T
MutationAssessor	Benign	1.0	L
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.88	N
REVEL	Uncertain	0.40
Sift	Benign	0.18	T
Sift4G	Benign	0.78	T
Polyphen		0.14	B
Vest4		0.53
MutPred		0.57		Gain of ubiquitination at E81 (P = 0.0117);
MVP		0.75
MPC		0.21
ClinPred		0.41	T
GERP RS		5.8
Varity_R		0.17
gMVP		0.57

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

LitVar

Other links and lift over

dbSNP: rs1034995435; hg19: chr7-20406662;