rs10239099

Positions:

• chr7-20369251-G-C
• chr7-20369251-G-T

Variant summary

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

The NM_002214.3(ITGB8):​c.388+2065G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 151,936 control chromosomes in the GnomAD database, including 5,941 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 0.27 (5941 hom., cov: 32)
• Consequence: ITGB8 NM_002214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760

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 = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB8	NM_002214.3	c.388+2065G>C		intron_variant		ENST00000222573.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB8	ENST00000222573.5	c.388+2065G>C		intron_variant		1	NM_002214.3	P1
ITGB8	ENST00000477859.1	n.2542+2065G>C		intron_variant, non_coding_transcript_variant		1
ITGB8	ENST00000478974.1	n.1093+2065G>C		intron_variant, non_coding_transcript_variant		1
ITGB8	ENST00000537992.5	c.-18+2065G>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40370 AN: 151818 Hom.: 5940 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.266 AC: 40382 AN: 151936 Hom.: 5941 Cov.: 32 AF XY: 0.263 AC XY: 19553 AN XY: 74266

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.287

Alfa AF: 0.182 Hom.: 440

Bravo AF: 0.250

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.5
DANN	Benign	0.51

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: rs10239099; hg19: chr7-20408874;