chr7-20379206-C-A

Variant names:

• chr7-20379206-C-A
• rs147908281
• NM_002214.3:c.544C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002214.3(ITGB8):​c.544C>A​(p.Arg182Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: ITGB8 NM_002214.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.660

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.083081424).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB8	NM_002214.3	c.544C>A	p.Arg182Ser	missense_variant	Exon 4 of 14	ENST00000222573.5	NP_002205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB8	ENST00000222573.5	c.544C>A	p.Arg182Ser	missense_variant	Exon 4 of 14	1	NM_002214.3	ENSP00000222573.3
ITGB8	ENST00000477859.1	n.2698C>A		non_coding_transcript_exon_variant	Exon 2 of 2	1
ITGB8	ENST00000478974.1	n.1249C>A		non_coding_transcript_exon_variant	Exon 4 of 9	1
ITGB8	ENST00000537992.5	c.139C>A	p.Arg47Ser	missense_variant	Exon 5 of 15	2		ENSP00000441561.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	11
DANN	Benign	0.74
DEOGEN2	Benign	0.37	.;T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.44	T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.083	T;T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	-1.6	.;N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	2.5	N;N
REVEL	Uncertain	0.33
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0010	.;B
Vest4		0.12
MutPred		0.55		.;Loss of MoRF binding (P = 0.0195);
MVP		0.26
MPC		0.16
ClinPred		0.067	T
GERP RS		4.9
Varity_R		0.41
gMVP		0.28

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

Other links and lift over

dbSNP: rs147908281; hg19: chr7-20418829;