7-20336395-A-G

Variant names:

• chr7-20336395-A-G
• rs10486391
• NM_002214.3:c.127+4462A>G

Variant summary

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

The NM_002214.3(ITGB8):​c.127+4462A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,048 control chromosomes in the GnomAD database, including 10,733 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 0.37 (10733 hom., cov: 32)
• Consequence: ITGB8 NM_002214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502
• Publications: 14 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

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.127+4462A>G		intron	N/A	NP_002205.1	P26012-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB8	ENST00000222573.5	TSL:1 MANE Select	c.127+4462A>G		intron	N/A	ENSP00000222573.3	P26012-1
	ITGB8	ENST00000460204.1	TSL:1	n.47+4372A>G		intron	N/A
	ITGB8	ENST00000478974.1	TSL:1	n.832+4462A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55925 AN: 151930 Hom.: 10740 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.368 AC: 55915 AN: 152048 Hom.: 10733 Cov.: 32 AF XY: 0.367 AC XY: 27283 AN XY: 74314

African (AFR) AF: 0.297 AC: 12313 AN: 41462

American (AMR) AF: 0.277 AC: 4233 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1511 AN: 3466

East Asian (EAS) AF: 0.343 AC: 1775 AN: 5170

South Asian (SAS) AF: 0.233 AC: 1124 AN: 4816

European-Finnish (FIN) AF: 0.467 AC: 4925 AN: 10552

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.423 AC: 28731 AN: 67976

Other (OTH) AF: 0.388 AC: 820 AN: 2112

Alfa AF: 0.400 Hom.: 47739

Bravo AF: 0.351

Asia WGS AF: 0.268 AC: 930 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.93
DANN	Benign	0.39
PhyloP100		-0.50
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: rs10486391; hg19: chr7-20376018;