NM_002214.3:c.37T>C

Variant names:

• chr7-20331843-T-C
• rs1784410381
• NM_002214.3:c.37T>C

Variant summary

Our verdict is Likely benign. The variant received -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. 17/22 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
• Publications: 0 publications found

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-AS1 (HGNC:55257): (ITGB8 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.035636634).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002214.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB8	NM_002214.3	MANE Select	c.37T>C	p.Phe13Leu	missense	Exon 1 of 14	NP_002205.1	P26012-1
	ITGB8-AS1	NR_110119.1		n.-81A>G		upstream_gene	N/A
	ITGB8-AS1	NR_110120.1		n.-81A>G		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB8	ENST00000222573.5	TSL:1 MANE Select	c.37T>C	p.Phe13Leu	missense	Exon 1 of 14	ENSP00000222573.3	P26012-1
	ITGB8	ENST00000478974.1	TSL:1	n.742T>C		non_coding_transcript_exon	Exon 1 of 9
	ITGB8	ENST00000897604.1		c.37T>C	p.Phe13Leu	missense	Exon 2 of 15	ENSP00000567663.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-0.11
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
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs1784410381; hg19: chr7-20371466;