rs3809865

Positions:

• chr17-47311220-T-A
• chr17-47311220-T-C
• chr17-47311220-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000212.3(ITGB3):​c.*1016T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 154,644 control chromosomes in the GnomAD database, including 38,174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (37521 hom., cov: 31)
  • Exomes 𝑓: 0.70 (653 hom.)
• Consequence: ITGB3 NM_000212.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.361

Genes affected

ITGB3 (HGNC:6156): (integrin subunit beta 3) The ITGB3 protein product is the integrin beta chain beta 3. Integrins are integral cell-surface proteins composed of an alpha chain and a beta chain. A given chain may combine with multiple partners resulting in different integrins. Integrin beta 3 is found along with the alpha IIb chain in platelets. Integrins are known to participate in cell adhesion as well as cell-surface mediated signalling. [provided by RefSeq, Jul 2008]

EFCAB13-DT (HGNC:55338): (EFCAB13 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-47311220-T-A is Benign according to our data. Variant chr17-47311220-T-A is described in ClinVar as [Benign]. Clinvar id is 323891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB3	NM_000212.3	c.*1016T>A		3_prime_UTR_variant	15/15	ENST00000559488.7
EFCAB13-DT	NR_110880.1	n.362+7252A>T		intron_variant, non_coding_transcript_variant
EFCAB13-DT	NR_110881.1	n.226+7252A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB3	ENST00000559488.7	c.*1016T>A		3_prime_UTR_variant	15/15	1	NM_000212.3	P1
EFCAB13-DT	ENST00000575039.1	n.226+7252A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106432 AN: 151930 Hom.: 37502 Cov.: 31

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.752

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.707

GnomAD4 exome AF: 0.701 AC: 1820 AN: 2596 Hom.: 653 Cov.: 0 AF XY: 0.705 AC XY: 1024 AN XY: 1452

Gnomad4 AFR exome AF: 0.660

Gnomad4 AMR exome AF: 0.519

Gnomad4 ASJ exome AF: 0.703

Gnomad4 EAS exome AF: 0.768

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.694

Gnomad4 NFE exome AF: 0.696

Gnomad4 OTH exome AF: 0.746

GnomAD4 genome AF: 0.700 AC: 106501 AN: 152048 Hom.: 37521 Cov.: 31 AF XY: 0.699 AC XY: 51950 AN XY: 74318

Gnomad4 AFR AF: 0.717

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.719

Gnomad4 EAS AF: 0.807

Gnomad4 SAS AF: 0.736

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.704

Alfa AF: 0.593 Hom.: 1688

Bravo AF: 0.696

Asia WGS AF: 0.725 AC: 2518 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Glanzmann thrombasthenia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 28, 2020

This variant is associated with the following publications: (PMID: 23451109) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.2
DANN	Benign	0.77

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: rs3809865; hg19: chr17-45388586;