rs10251386

Variant names:

• chr7-20358284-T-C
• rs10251386
• NM_002214.3:c.128-5353T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002214.3(ITGB8):​c.128-5353T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,032 control chromosomes in the GnomAD database, including 4,755 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4755 hom., cov: 31)
• Consequence: ITGB8 NM_002214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• Publications: 5 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB8	NM_002214.3	c.128-5353T>C		intron_variant	Intron 1 of 13	ENST00000222573.5	NP_002205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB8	ENST00000222573.5	c.128-5353T>C		intron_variant	Intron 1 of 13	1	NM_002214.3	ENSP00000222573.3
ITGB8	ENST00000478974.1	n.833-5353T>C		intron_variant	Intron 1 of 8	1
ITGB8	ENST00000537992.5	c.-278-5353T>C		intron_variant	Intron 2 of 14	2		ENSP00000441561.1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35597 AN: 151914 Hom.: 4755 Cov.: 31

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.254

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.234 AC: 35598 AN: 152032 Hom.: 4755 Cov.: 31 AF XY: 0.234 AC XY: 17411 AN XY: 74336

African (AFR) AF: 0.168 AC: 6955 AN: 41482

American (AMR) AF: 0.182 AC: 2776 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1027 AN: 3468

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5184

South Asian (SAS) AF: 0.113 AC: 542 AN: 4806

European-Finnish (FIN) AF: 0.364 AC: 3845 AN: 10576

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19624 AN: 67916

Other (OTH) AF: 0.251 AC: 531 AN: 2114

Alfa AF: 0.250 Hom.: 847

Bravo AF: 0.215

Asia WGS AF: 0.0590 AC: 206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.83
DANN	Benign	0.59
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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: rs10251386; hg19: chr7-20397907;