chr7-20363688-C-G

Variant names:

• chr7-20363688-C-G
• NM_002214.3:c.179C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002214.3(ITGB8):​c.179C>G​(p.Ala60Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ITGB8 NM_002214.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37461978).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB8	NM_002214.3	c.179C>G	p.Ala60Gly	missense_variant	Exon 2 of 14	ENST00000222573.5	NP_002205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB8	ENST00000222573.5	c.179C>G	p.Ala60Gly	missense_variant	Exon 2 of 14	1	NM_002214.3	ENSP00000222573.3
ITGB8	ENST00000478974.1	n.884C>G		non_coding_transcript_exon_variant	Exon 2 of 9	1
ITGB8	ENST00000537992	c.-227C>G		5_prime_UTR_variant	Exon 3 of 15	2		ENSP00000441561.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453138 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 722880

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.72	D
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.37	T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.37
Sift	Benign	0.24	T
Sift4G	Benign	0.41	T
Polyphen		0.72	P
Vest4		0.31
MutPred		0.58		Loss of stability (P = 0.0811);
MVP		0.76
MPC		0.15
ClinPred		0.58	D
GERP RS		1.2
Varity_R		0.077
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-20403311;