10-32923577-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002211.4(ITGB1):c.942+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00977 in 1,603,052 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0076 (7 hom., cov: 32)
  • Exomes 𝑓: 0.010 (105 hom.)
• Consequence: ITGB1 NM_002211.4 splice_region, intron
• Scores: Splicing: ADA: 0.0001650
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.701

Genes affected

ITGB1 (HGNC:6153): (integrin subunit beta 1) Integrins are heterodimeric proteins made up of alpha and beta subunits. At least 18 alpha and 8 beta subunits have been described in mammals. Integrin family members are membrane receptors involved in cell adhesion and recognition in a variety of processes including embryogenesis, hemostasis, tissue repair, immune response and metastatic diffusion of tumor cells. This gene encodes a beta subunit. Multiple alternatively spliced transcript variants which encode different protein isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 10-32923577-G-A is Benign according to our data. Variant chr10-32923577-G-A is described in ClinVar as [Benign]. Clinvar id is 773233.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-32923577-G-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00764 (1163/152182) while in subpopulation SAS AF= 0.0189 (91/4808). AF 95% confidence interval is 0.0158. There are 7 homozygotes in gnomad4. There are 566 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1163 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB1	NM_002211.4	c.942+8C>T		splice_region_variant, intron_variant		ENST00000302278.8
ITGB1	NM_033668.2	c.942+8C>T		splice_region_variant, intron_variant
ITGB1	NM_133376.3	c.942+8C>T		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB1	ENST00000302278.8	c.942+8C>T		splice_region_variant, intron_variant		1	NM_002211.4	P4

Frequencies

GnomAD3 genomes AF: 0.00765 AC: 1163 AN: 152064 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00498

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0189

Gnomad FIN AF: 0.0147

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00963

Gnomad OTH AF: 0.00910

GnomAD3 exomes AF: 0.00978 AC: 2414 AN: 246818 Hom.: 14 AF XY: 0.0108 AC XY: 1435 AN XY: 133356

Gnomad AFR exome AF: 0.00230

Gnomad AMR exome AF: 0.00513

Gnomad ASJ exome AF: 0.0168

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0192

Gnomad FIN exome AF: 0.0137

Gnomad NFE exome AF: 0.00983

Gnomad OTH exome AF: 0.0126

GnomAD4 exome AF: 0.00999 AC: 14493 AN: 1450870 Hom.: 105 Cov.: 29 AF XY: 0.0104 AC XY: 7528 AN XY: 721556

Gnomad4 AFR exome AF: 0.00247

Gnomad4 AMR exome AF: 0.00585

Gnomad4 ASJ exome AF: 0.0169

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0202

Gnomad4 FIN exome AF: 0.0132

Gnomad4 NFE exome AF: 0.00944

Gnomad4 OTH exome AF: 0.0112

GnomAD4 genome AF: 0.00764 AC: 1163 AN: 152182 Hom.: 7 Cov.: 32 AF XY: 0.00761 AC XY: 566 AN XY: 74406

Gnomad4 AFR AF: 0.00265

Gnomad4 AMR AF: 0.00497

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0189

Gnomad4 FIN AF: 0.0147

Gnomad4 NFE AF: 0.00965

Gnomad4 OTH AF: 0.00900

Alfa AF: 0.00953 Hom.: 4

Bravo AF: 0.00667

Asia WGS AF: 0.00693 AC: 24 AN: 3478

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

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	7.1
Dann	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00017
dbscSNV1_RF	Benign	0.0
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: rs56339866; hg19: chr10-33212505;