7-20336395-A-G

Position:

• chr7-20336395-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000222573.5(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 ENST00000222573.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB8	NM_002214.3	c.127+4462A>G		intron_variant		ENST00000222573.5	NP_002205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB8	ENST00000222573.5	c.127+4462A>G		intron_variant		1	NM_002214.3	ENSP00000222573	P1
ITGB8	ENST00000460204.1	n.47+4372A>G		intron_variant, non_coding_transcript_variant		1
ITGB8	ENST00000478974.1	n.832+4462A>G		intron_variant, non_coding_transcript_variant		1
ITGB8	ENST00000537992.5	c.-279+4372A>G		intron_variant		2		ENSP00000441561

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

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.388

Alfa AF: 0.405 Hom.: 20083

Bravo AF: 0.351

Asia WGS AF: 0.268 AC: 930 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.93
DANN	Benign	0.39

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: rs10486391; hg19: chr7-20376018;