rs3779505

Variant names:

• chr7-20365642-G-A
• rs3779505
• ENST00000477859.1:n.998G>A

Variant summary

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

The ENST00000477859.1(ITGB8):​n.998G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,214 control chromosomes in the GnomAD database, including 1,217 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 0.11 (1216 hom., cov: 32)
  • Exomes 𝑓: 0.075 (1 hom.)
• Consequence: ITGB8 ENST00000477859.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113
• Publications: 7 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000477859.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB8	NM_002214.3	MANE Select	c.214-1370G>A		intron	N/A	NP_002205.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB8	ENST00000477859.1	TSL:1	n.998G>A		non_coding_transcript_exon	Exon 1 of 2
	ITGB8	ENST00000222573.5	TSL:1 MANE Select	c.214-1370G>A		intron	N/A	ENSP00000222573.3
	ITGB8	ENST00000478974.1	TSL:1	n.919-1370G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17267 AN: 152056 Hom.: 1215 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.0815

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.0750 AC: 3 AN: 40 Hom.: 1 Cov.: 0 AF XY: 0.115 AC XY: 3 AN XY: 26

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0833 AC: 3 AN: 36

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.113 AC: 17262 AN: 152174 Hom.: 1216 Cov.: 32 AF XY: 0.116 AC XY: 8598 AN XY: 74402

African (AFR) AF: 0.108 AC: 4474 AN: 41516

American (AMR) AF: 0.0815 AC: 1247 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 372 AN: 3466

East Asian (EAS) AF: 0.412 AC: 2130 AN: 5170

South Asian (SAS) AF: 0.119 AC: 573 AN: 4820

European-Finnish (FIN) AF: 0.102 AC: 1082 AN: 10598

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6983 AN: 67994

Other (OTH) AF: 0.105 AC: 222 AN: 2114

Alfa AF: 0.107 Hom.: 524

Bravo AF: 0.114

Asia WGS AF: 0.226 AC: 784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.67
PhyloP100		-0.11
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: rs3779505; hg19: chr7-20405265;