7-20331938-G-GTTGTT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_002214.3(ITGB8):c.127+23_127+27dup variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,614,026 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (2 hom., cov: 34)
  • Exomes 𝑓: 0.0015 (4 hom.)
• Consequence: ITGB8 NM_002214.3 splice_donor_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.86

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 7-20331938-G-GTTGTT is Benign according to our data. Variant chr7-20331938-G-GTTGTT is described in ClinVar as [Benign]. Clinvar id is 2041445.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 359 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB8	NM_002214.3	c.127+23_127+27dup		splice_donor_region_variant, intron_variant		ENST00000222573.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB8	ENST00000222573.5	c.127+23_127+27dup		splice_donor_region_variant, intron_variant		1	NM_002214.3	P1
ITGB8	ENST00000478974.1	n.832+23_832+27dup		splice_donor_region_variant, intron_variant, non_coding_transcript_variant		1
ITGB8	ENST00000537992.5	c.-325-21_-325-17dup		intron_variant		2
ITGB8	ENST00000460204.1			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.00236 AC: 359 AN: 152268 Hom.: 2 Cov.: 34

Gnomad AFR AF: 0.000313

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00154

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00233 AC: 578 AN: 248080 Hom.: 1 AF XY: 0.00194 AC XY: 261 AN XY: 134348

Gnomad AFR exome AF: 0.000555

Gnomad AMR exome AF: 0.00934

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.000817

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000927

Gnomad NFE exome AF: 0.00169

Gnomad OTH exome AF: 0.00197

GnomAD4 exome AF: 0.00154 AC: 2255 AN: 1461640 Hom.: 4 Cov.: 33 AF XY: 0.00141 AC XY: 1025 AN XY: 727124

Gnomad4 AFR exome AF: 0.000299

Gnomad4 AMR exome AF: 0.00895

Gnomad4 ASJ exome AF: 0.000727

Gnomad4 EAS exome AF: 0.000554

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.000955

Gnomad4 NFE exome AF: 0.00152

Gnomad4 OTH exome AF: 0.000977

GnomAD4 genome AF: 0.00235 AC: 358 AN: 152386 Hom.: 2 Cov.: 34 AF XY: 0.00271 AC XY: 202 AN XY: 74518

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.0127

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00141

Gnomad4 NFE AF: 0.00153

Gnomad4 OTH AF: 0.00284

Bravo AF: 0.00261

EpiCase AF: 0.00120

EpiControl AF: 0.00119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs577437870; hg19: chr7-20371561;