7-20331843-T-C

Position:

• chr7-20331843-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002214.3(ITGB8):​c.37T>C​(p.Phe13Leu) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: ITGB8 NM_002214.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.114

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
• BP4: Computational evidence support a benign effect (MetaRNN=0.035636634).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB8	NM_002214.3	c.37T>C	p.Phe13Leu	missense_variant	1/14	ENST00000222573.5	NP_002205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB8	ENST00000222573.5	c.37T>C	p.Phe13Leu	missense_variant	1/14	1	NM_002214.3	ENSP00000222573.3
ITGB8	ENST00000478974.1	n.742T>C		non_coding_transcript_exon_variant	1/9	1
ITGB8	ENST00000537992.5	c.-325-134T>C		intron_variant		2		ENSP00000441561.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 05, 2024

The c.37T>C (p.F13L) alteration is located in exon 1 (coding exon 1) of the ITGB8 gene. This alteration results from a T to C substitution at nucleotide position 37, causing the phenylalanine (F) at amino acid position 13 to be replaced by a leucine (L). 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	0.28
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	2.3
DANN	Benign	0.46
DEOGEN2	Benign	0.14	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.34	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.21
Sift	Benign	0.79	T
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.063
MutPred		0.30		Loss of catalytic residue at F13 (P = 0.0135);
MVP		0.33
MPC		0.17
ClinPred		0.078	T
GERP RS		-2.9
Varity_R		0.037
gMVP		0.42

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: rs1784410381; hg19: chr7-20371466;